SMAD6 — 1233 ClinVar variants

All ClinVar germline SMAD6 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 655 flagged for review →

37 Pathogenic · 4 Pathogenic/Likely pathogenic · 33 Likely pathogenic · 57 Conflicting · 14 Benign · 13 Benign/Likely benign · 281 Likely benign · 794 Uncertain significance

Full SMAD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 655

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 3

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

SMAD6 p.Gly154Asp Likely pathogenic No assertion criteria
congenital radioulnar synostosis
SMAD6 p.Gly29Ala Likely pathogenic No assertion criteria
thoracic aortic aneurysm
SMAD6 p.Pro257Leu Pathogenic No assertion criteria
aortic valve disease 1

Predictors agree, ClinVar conflicts 21

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

SMAD6 p.Ala161Val Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Ala254Asp Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Ala325Thr Conflicting Single submitter
craniosynostosis 7
SMAD6 p.Arg231Pro Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Arg285Cys Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Arg285His Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Arg75Gln Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Arg85Cys Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Asp36Asn Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Cys121Tyr Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Glu442Lys Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Gly433Ser Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Lys395Arg Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Pro323Ser Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Pro65Arg Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Pro65Ser Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Ser333Thr Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Ser58Cys Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Trp14Arg Conflicting Single submitter
SMAD6 p.Val239Met Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Leu191Pro Conflicting No assertion criteria
congenital radioulnar synostosis

Predictors lean, ClinVar uncertain 527

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 527

SMAD6 p.Ala100Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala100Thr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala134Thr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala135Thr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala161Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala211Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala211Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala253Thr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala424Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala449Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ala454Pro Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala455Thr Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala469Pro Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala80Val Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala86Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg12Gln Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg132Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg139Trp Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg157Trp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg17His Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg182Trp Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg198Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg228Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg231Cys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg268Trp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg281Trp Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg428His Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg42Gln Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg443Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg465Cys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg478Gln Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg6Cys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg82Lys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg83Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg84Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg84Trp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asn404Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp106Asn Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp143Glu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp212Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp255Ala Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp286Asn Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp286Gly Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp359His Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp36Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp36Tyr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp36Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp70Glu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Asp70Val Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Cys205Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Cys261Gly Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Cys261Tyr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Cys484Tyr Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gln362Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gln74His Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Glu118Lys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Glu151Asp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Glu185Lys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Glu24Gly Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Glu35Gly Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Glu489Lys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Glu51Asp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly111Glu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly147Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly155Cys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly156Arg Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly156Trp Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly200Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly204Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly28Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly31Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly33Cys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly471Val Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly81Glu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly87Trp Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly88Cys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Gly99Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.His265Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.His265Tyr Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ile310Val Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ile410Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu116Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu145Pro Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Leu229Val Uncertain significance Multiple submitters
SMAD6-related disease
SMAD6 p.Leu244Pro Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Leu244Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu269Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu368Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu392Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu393Pro Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Leu9Val Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Met321Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Met93Ile Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Met93Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Met93Thr Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro110Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro117Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro138Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro144Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro144Thr Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro202Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro222Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro222Gln Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro233Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro263Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro272Ala Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro284Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro313Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro323Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro415Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro450Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro450Thr Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro452Arg Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro45Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro461Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro62Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro65Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro68Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro89Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro90Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser130Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser158Arg Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ser158Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ser163Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser178Trp Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser267Arg Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ser27Asn Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser333Asn Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ser483Phe Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser58Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Thr303Met Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Thr326Ala Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Thr383Met Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Thr482Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Tyr336His Uncertain significance Multiple submitters
SMAD6-related disease
SMAD6 p.Val18Gly Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val195Met Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val19Phe Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val259Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val400Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val400Met Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val426Ile Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Val60Ile Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ala100Ser Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ala100Val Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ala108Gly Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ala108Val Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ala134Val Uncertain significance Single submitter
SMAD6 p.Ala135Ser Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ala141Gly Uncertain significance Single submitter
aortic valve disease 2

Predictors split 104

The independent predictors disagree with each other — read with care.

SMAD6 p.Arg11Gln Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg15Gly Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg210Cys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg214His Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg281Gln Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg3Lys Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Arg428Cys Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg91Met Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asn462Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp292Asn Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Asp440Asn Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Gly203Arg Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.His408Gln Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Ile356Val Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Leu13Phe Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu226Phe Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Leu373Pro Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro243Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro278Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro278Ser Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro328Leu Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro397His Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro397Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Pro409Ser Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Pro432Ala Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser16Asn Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Ser444Leu Uncertain significance Multiple submitters
Inborn genetic diseases
SMAD6 p.Thr341Met Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Tyr434His Uncertain significance Multiple submitters
aortic valve disease 2
SMAD6 p.Arg11Gly Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg162Pro Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg198Cys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg214Cys Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg214Gly Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg214Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg281Gly Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Arg281Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg376His Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg381Gly Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg382Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg3Ser Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg423His Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg443Cys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Arg443Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg496Ile Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Arg50Ile Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Asn262Ser Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Asp189His Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Asp255Asn Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Asp359Glu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Asp398Asn Uncertain significance Single submitter
SMAD6 p.Glu169Lys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Glu171Asp Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Glu196Asp Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Glu407Gly Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Glu407Lys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Gly217Cys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Gly29Asp Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Gly29Val Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Gly363Ser Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Gly406Cys Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Gly422Asp Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.His339Leu Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Ile436Val Uncertain significance Single submitter
SMAD6 p.Leu13Val Uncertain significance Single submitter
SMAD6 p.Leu172Phe Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Leu207Arg Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Leu241Val Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Leu360Val Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Lys173Asn Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Lys386Arg Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Phe266Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Phe441Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Pro221Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Pro221Ser Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Pro290Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Pro458Arg Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Pro458Ser Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Pro461Ala Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ser178Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ser249Arg Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ser267Thr Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Ser280Cys Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ser283Pro Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ser296Phe Conflicting Single submitter
craniosynostosis 7
SMAD6 p.Ser299Cys Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Ser322Phe Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ser333Cys Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Ser385Asn Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Thr125Ile Conflicting Single submitter
aortic valve disease 2
SMAD6 p.Thr176Met Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Thr341Ala Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Tyr300His Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Tyr358Asn Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Tyr434Cys Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Tyr459Asn Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Val10Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Val124Met Uncertain significance Single submitter
SMAD6 p.Val206Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Val259Ala Conflicting Single submitter
Inborn genetic diseases
SMAD6 p.Val334Leu Uncertain significance Single submitter
aortic valve disease 2
SMAD6 p.Val343Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Val354Leu Uncertain significance Single submitter
Inborn genetic diseases
SMAD6 p.Val430Leu Uncertain significance Single submitter
Inborn genetic diseases

All SMAD6 variants

Pathogenic 37

c.953-1G>A Single submitter
p.Cys484Phe Single submitter craniosynostosis 7
p.Glu273Gln Single submitter
p.Glu35Ter Single submitter aortic valve disease 2
p.Gly156fs Single submitter aortic valve disease 2
p.Leu298fs Single submitter
p.Pro290fs Single submitter aortic valve disease 2
p.Trp115Ter Single submitter cardiogenetic disease
p.Ala153fs No assertion criteria congenital radioulnar synostosis
p.Asp36fs No assertion criteria congenital radioulnar synostosis
p.Cys367fs No assertion criteria congenital radioulnar synostosis
p.Cys475fs No assertion criteria congenital radioulnar synostosis
p.Cys55Ter No assertion criteria Abnormal axial skeleton morphology
p.Glu109fs No assertion criteria congenital radioulnar synostosis
p.Glu171Lys No assertion criteria congenital radioulnar synostosis
p.Glu23fs No assertion criteria congenital radioulnar synostosis
p.Glu287Ter No assertion criteria congenital radioulnar synostosis
p.Glu315Ter No assertion criteria congenital radioulnar synostosis
p.Glu338Ter No assertion criteria congenital radioulnar synostosis
p.Glu378Ter No assertion criteria congenital radioulnar synostosis
p.Glu95fs No assertion criteria congenital radioulnar synostosis
p.Gly390_Ile391dup No assertion criteria aortic valve disease 2
p.Gly73Ter No assertion criteria congenital radioulnar synostosis
p.Gly99fs No assertion criteria Plagiocephaly
p.Ile410fs No assertion criteria polydactyly
p.Leu291fs No assertion criteria congenital radioulnar synostosis
p.Leu9fs No assertion criteria congenital radioulnar synostosis
p.Lys429Ter No assertion criteria Frontal bossing
p.Lys437Ter No assertion criteria congenital radioulnar synostosis
p.Phe2fs No assertion criteria congenital radioulnar synostosis
p.Pro257Leu No assertion criteria aortic valve disease 1 ⚠
p.Ser197fs No assertion criteria congenital radioulnar synostosis
p.Ser320fs No assertion criteria congenital radioulnar synostosis
p.Trp337Ter No assertion criteria congenital radioulnar synostosis
p.Trp472Ter No assertion criteria congenital radioulnar synostosis
p.Val195Gly No assertion criteria craniosynostosis 7
p.Val259fs No assertion criteria

Pathogenic/Likely pathogenic 4

p.Gln218Ter Multiple submitters aortic valve disease 2
p.Gln78fs Multiple submitters aortic valve disease 2
p.Ser158fs Multiple submitters aortic valve disease 2
p.Tyr264Ter Multiple submitters aortic valve disease 2

Likely pathogenic 33

p.Gln370Ter Multiple submitters Autosomal dominant SMAD6-related disorders
p.Ala305fs Single submitter Inborn genetic diseases
p.Ala312fs Single submitter aortic valve disease 2
p.Ala46fs Single submitter congenital radioulnar synostosis
p.Arg231fs Single submitter aortic valve disease 2
p.Arg405fs Single submitter aortic valve disease 2
p.Arg82fs Single submitter radioulnar synostosis, nonsyndromic, susceptibility to
p.Asn413fs Single submitter
p.Asp453fs Single submitter
p.Cys270Ter Single submitter
p.Gln218fs Single submitter
p.Glu407Ter Single submitter
p.Gly388fs Single submitter craniosynostosis 7
p.Gly53Ter Single submitter aortic valve disease 2
p.Gly81fs Single submitter congenital radioulnar synostosis
p.Ile436fs Single submitter congenital radioulnar synostosis
p.Ile481fs Single submitter aortic valve disease 2
p.Leu145fs Single submitter
p.Lys289Ter Single submitter aortic valve disease 2
p.Phe357Ile Single submitter
p.Pro152fs Single submitter SMAD6-related disease
p.Pro277fs Single submitter
p.Pro65fs Single submitter craniosynostosis 7
p.Ser317Ter Single submitter Inborn genetic diseases
p.Trp14fs Single submitter
p.Trp232Ter Single submitter
p.Tyr336Ter Single submitter
p.Arg198fs No assertion criteria craniosynostosis 7
p.Glu185fs No assertion criteria SMAD6-related disease
p.Gly154Asp No assertion criteria congenital radioulnar synostosis ⚠
p.Gly29Ala No assertion criteria thoracic aortic aneurysm ⚠
p.Leu13His No assertion criteria congenital radioulnar synostosis
p.Ser197Tyr No assertion criteria congenital radioulnar synostosis

Conflicting classifications of pathogenicity 57

c.818-1G>A Single submitter aortic valve disease 2
c.874+4A>G Single submitter aortic valve disease 2
c.874+8_874+9del Single submitter radioulnar synostosis, nonsyndromic, susceptibility to
p.Ala135_Ala141del Single submitter aortic valve disease 2
p.Ala161Val Single submitter Inborn genetic diseases ⚠
p.Ala254Asp Single submitter Inborn genetic diseases ⚠
p.Ala325Thr Single submitter craniosynostosis 7 ⚠
p.Arg12Ter Single submitter aortic valve disease 2
p.Arg15Ter Single submitter aortic valve disease 2
p.Arg231Pro Single submitter aortic valve disease 2 ⚠
p.Arg281fs Single submitter Inborn genetic diseases
p.Arg281Gly Single submitter Inborn genetic diseases ⚠
p.Arg285Cys Single submitter Inborn genetic diseases ⚠
p.Arg285His Single submitter aortic valve disease 2 ⚠
p.Arg382Ter Single submitter aortic valve disease 2
p.Arg42Ter Single submitter aortic valve disease 2
p.Arg75Gln Single submitter aortic valve disease 2 ⚠
p.Arg75Ter Single submitter aortic valve disease 2
p.Arg84fs Single submitter aortic valve disease 2
p.Arg85Cys Single submitter aortic valve disease 2 ⚠
p.Asp212fs Single submitter aortic valve disease 2
p.Asp36Asn Single submitter aortic valve disease 2 ⚠
p.Cys121Tyr Single submitter aortic valve disease 2 ⚠
p.Cys205fs Single submitter aortic valve disease 2
p.Gln170Ter Single submitter aortic valve disease 2
p.Gln223Ter Single submitter aortic valve disease 2
p.Gln236Ter Single submitter aortic valve disease 2
p.Gln362Ter Single submitter aortic valve disease 2
p.Glu171fs Single submitter radioulnar synostosis, nonsyndromic, susceptibility to
p.Glu171Ter Single submitter aortic valve disease 2
p.Glu273Ter Single submitter aortic valve disease 2
p.Glu442Lys Single submitter aortic valve disease 2 ⚠
p.Gly433fs Single submitter craniosynostosis 7
p.Gly433Ser Single submitter aortic valve disease 2 ⚠
p.Gly88fs Single submitter radioulnar synostosis, nonsyndromic, susceptibility to
p.His339Leu Single submitter aortic valve disease 2 ⚠
p.Lys395Arg Single submitter aortic valve disease 2 ⚠
p.Met1Thr Single submitter aortic valve disease 2
p.Pro323Ser Single submitter Inborn genetic diseases ⚠
p.Pro65Arg Single submitter Inborn genetic diseases ⚠
p.Pro65Ser Single submitter Inborn genetic diseases ⚠
p.Ser130fs Single submitter aortic valve disease 2
p.Ser130Ter Single submitter aortic valve disease 2
p.Ser178Ter Single submitter aortic valve disease 2
p.Ser27_Gly28del Single submitter aortic valve disease 2
p.Ser296Phe Single submitter craniosynostosis 7 ⚠
p.Ser299Cys Single submitter aortic valve disease 2 ⚠
p.Ser333Thr Single submitter aortic valve disease 2 ⚠
p.Ser58Cys Single submitter aortic valve disease 2 ⚠
p.Thr125Ile Single submitter aortic valve disease 2 ⚠
p.Trp14Arg Single submitter ⚠
p.Trp14Ter Single submitter aortic valve disease 2
p.Tyr177Ter Single submitter aortic valve disease 2
p.Val239Met Single submitter aortic valve disease 2 ⚠
p.Val259Ala Single submitter Inborn genetic diseases ⚠
p.His265fs No assertion criteria aortic valve disease 1
p.Leu191Pro No assertion criteria congenital radioulnar synostosis ⚠

Benign 14

c.817+113C>T Multiple submitters
c.817+55C>A Multiple submitters
c.817+9G>C Multiple submitters aortic valve disease 2
c.818-165C>T Multiple submitters
c.875-22C>A Multiple submitters aortic valve disease 2
c.875-51G>A Multiple submitters
c.-274G>A Multiple submitters
c.-767C>T Multiple submitters
c.*23G>T Multiple submitters
p.Phe389= Multiple submitters aortic valve disease 2
c.818-2679G>A Single submitter
c.818-3394A>T Single submitter
c.874+272G>A Single submitter
c.*2GGC[1] Single submitter

Benign/Likely benign 13

c.952+13del Multiple submitters craniosynostosis 7
p.Ala135= Multiple submitters Inborn genetic diseases
p.Arg285= Multiple submitters Inborn genetic diseases
p.Asp21Asn Multiple submitters Inborn genetic diseases
p.Asp286= Multiple submitters Inborn genetic diseases
p.Asp453= Multiple submitters Inborn genetic diseases
p.Gly40= Multiple submitters Inborn genetic diseases
p.His237= Multiple submitters aortic valve disease 2
p.Pro397= Multiple submitters aortic valve disease 2
p.Pro420= Multiple submitters Inborn genetic diseases
p.Pro47Ser Multiple submitters aortic valve disease 2
p.Thr303= Multiple submitters Inborn genetic diseases
p.Val343= Multiple submitters Inborn genetic diseases

Likely benign 281

c.817+17G>C Multiple submitters aortic valve disease 2
c.-44C>T Multiple submitters
p.Ala137= Multiple submitters Inborn genetic diseases
p.Ala238= Multiple submitters aortic valve disease 2
p.Ala319Val Multiple submitters Inborn genetic diseases
p.Ala335= Multiple submitters aortic valve disease 2
p.Ala353= Multiple submitters aortic valve disease 2
p.Ala402= Multiple submitters aortic valve disease 2
p.Ala419= Multiple submitters Inborn genetic diseases
p.Ala419Val Multiple submitters Inborn genetic diseases
p.Ala449= Multiple submitters Inborn genetic diseases
p.Ala454= Multiple submitters Inborn genetic diseases
p.Ala455= Multiple submitters Inborn genetic diseases
p.Ala64= Multiple submitters aortic valve disease 2
p.Ala77= Multiple submitters aortic valve disease 2
p.Ala80= Multiple submitters aortic valve disease 2
p.Arg15= Multiple submitters Inborn genetic diseases
p.Arg162= Multiple submitters Inborn genetic diseases
p.Arg182= Multiple submitters Inborn genetic diseases
p.Arg198= Multiple submitters Inborn genetic diseases
p.Arg214= Multiple submitters aortic valve disease 2
p.Arg382= Multiple submitters Inborn genetic diseases
p.Arg443= Multiple submitters aortic valve disease 2
p.Arg48= Multiple submitters Inborn genetic diseases
p.Arg67= Multiple submitters Inborn genetic diseases
p.Asn493= Multiple submitters Inborn genetic diseases
p.Asp133= Multiple submitters Inborn genetic diseases
p.Asp21= Multiple submitters aortic valve disease 2
p.Asp212= Multiple submitters aortic valve disease 2
p.Asp234= Multiple submitters aortic valve disease 2
p.Asp255= Multiple submitters aortic valve disease 2
p.Asp318= Multiple submitters aortic valve disease 2
p.Asp34= Multiple submitters Inborn genetic diseases
p.Asp398= Multiple submitters Inborn genetic diseases
p.Asp70= Multiple submitters aortic valve disease 2
p.Cys245= Multiple submitters Inborn genetic diseases
p.Cys260= Multiple submitters Inborn genetic diseases
p.Cys367= Multiple submitters aortic valve disease 2
p.Cys484= Multiple submitters Inborn genetic diseases
p.Gln375= Multiple submitters Inborn genetic diseases
p.Glu24= Multiple submitters Inborn genetic diseases
p.Glu273= Multiple submitters Inborn genetic diseases
p.Glu35= Multiple submitters aortic valve disease 2
p.Gly112= Multiple submitters aortic valve disease 2
p.Gly114= Multiple submitters aortic valve disease 2
p.Gly203= Multiple submitters aortic valve disease 2
p.Gly217= Multiple submitters aortic valve disease 2
p.Gly25= Multiple submitters Inborn genetic diseases
p.Gly28= Multiple submitters Inborn genetic diseases
p.Gly421= Multiple submitters Inborn genetic diseases
p.Gly87= Multiple submitters Inborn genetic diseases
p.Gly97Glu Multiple submitters Inborn genetic diseases
p.Ile356= Multiple submitters aortic valve disease 2
p.Ile387= Multiple submitters Inborn genetic diseases
p.Ile391= Multiple submitters Inborn genetic diseases
p.Leu104= Multiple submitters Inborn genetic diseases
p.Leu128= Multiple submitters aortic valve disease 2
p.Leu165= Multiple submitters Inborn genetic diseases
p.Leu166= Multiple submitters Inborn genetic diseases
p.Leu167= Multiple submitters Inborn genetic diseases
p.Leu180= Multiple submitters aortic valve disease 2
p.Leu188= Multiple submitters aortic valve disease 2
p.Leu191= Multiple submitters Inborn genetic diseases
p.Leu215= Multiple submitters aortic valve disease 2
p.Leu224= Multiple submitters Inborn genetic diseases
p.Leu229= Multiple submitters Inborn genetic diseases
p.Leu235= Multiple submitters aortic valve disease 2
p.Leu241= Multiple submitters Inborn genetic diseases
p.Leu244= Multiple submitters Inborn genetic diseases
p.Leu269= Multiple submitters Inborn genetic diseases
p.Leu293= Multiple submitters aortic valve disease 2
p.Leu298= Multiple submitters Inborn genetic diseases
p.Leu9= Multiple submitters Inborn genetic diseases
p.Phe129= Multiple submitters Inborn genetic diseases
p.Phe266= Multiple submitters Inborn genetic diseases
p.Phe441= Multiple submitters Inborn genetic diseases
p.Pro138= Multiple submitters aortic valve disease 2
p.Pro202= Multiple submitters aortic valve disease 2
p.Pro209= Multiple submitters aortic valve disease 2
p.Pro263= Multiple submitters Inborn genetic diseases
p.Pro272= Multiple submitters Inborn genetic diseases
p.Pro275= Multiple submitters Inborn genetic diseases
p.Pro323= Multiple submitters aortic valve disease 2
p.Pro45= Multiple submitters Inborn genetic diseases
p.Pro450= Multiple submitters aortic valve disease 2
p.Pro47= Multiple submitters Inborn genetic diseases
p.Pro474= Multiple submitters Inborn genetic diseases
p.Pro65= Multiple submitters aortic valve disease 2
p.Pro68= Multiple submitters Inborn genetic diseases
p.Pro89= Multiple submitters aortic valve disease 2
p.Pro90= Multiple submitters Inborn genetic diseases
p.Pro92= Multiple submitters Inborn genetic diseases
p.Pro96= Multiple submitters Inborn genetic diseases
p.Ser187= Multiple submitters Inborn genetic diseases
p.Ser197= Multiple submitters Inborn genetic diseases
p.Ser249= Multiple submitters aortic valve disease 2
p.Ser27= Multiple submitters Inborn genetic diseases
p.Ser27Gly Multiple submitters Inborn genetic diseases
p.Ser294= Multiple submitters Inborn genetic diseases
p.Ser296= Multiple submitters Inborn genetic diseases
p.Ser379= Multiple submitters aortic valve disease 2
p.Ser477= Multiple submitters Inborn genetic diseases
p.Ser7= Multiple submitters aortic valve disease 2
p.Ser94= Multiple submitters Inborn genetic diseases
p.Thr125= Multiple submitters aortic valve disease 2
p.Thr176= Multiple submitters Inborn genetic diseases
p.Thr190= Multiple submitters Inborn genetic diseases
p.Thr297= Multiple submitters Inborn genetic diseases
p.Thr341= Multiple submitters aortic valve disease 2
p.Thr416= Multiple submitters aortic valve disease 2
p.Tyr177= Multiple submitters Inborn genetic diseases
p.Tyr358= Multiple submitters Inborn genetic diseases
p.Val195= Multiple submitters Inborn genetic diseases
p.Val206= Multiple submitters Inborn genetic diseases
p.Val412= Multiple submitters Inborn genetic diseases
p.Val60= Multiple submitters Inborn genetic diseases
p.Val60Phe Multiple submitters aortic valve disease 2
c.817+14G>A Single submitter aortic valve disease 2
c.817+16C>T Single submitter aortic valve disease 2
c.817+17G>A Single submitter aortic valve disease 2
c.817+18G>C Single submitter
c.818-11C>T Single submitter aortic valve disease 2
c.818-12C>T Single submitter aortic valve disease 2
c.818-17T>C Single submitter aortic valve disease 2
c.818-6T>C Single submitter aortic valve disease 2
c.818-8T>C Single submitter aortic valve disease 2
c.874+10C>T Single submitter aortic valve disease 2
c.874+12C>T Single submitter aortic valve disease 2
c.874+15C>A Single submitter aortic valve disease 2
c.874+15C>T Single submitter aortic valve disease 2
c.874+20T>G Single submitter aortic valve disease 2
c.874+8T>C Single submitter aortic valve disease 2
c.874+9G>A Single submitter
c.875-10C>T Single submitter aortic valve disease 2
c.875-14C>G Single submitter
c.875-9C>G Single submitter aortic valve disease 2
c.952+16T>C Single submitter aortic valve disease 2
c.952+8T>C Single submitter aortic valve disease 2
c.953-17dup Single submitter aortic valve disease 2
c.953-18C>A Single submitter aortic valve disease 2
c.953-19C>A Single submitter aortic valve disease 2
c.953-19C>G Single submitter
c.953-20T>C Single submitter aortic valve disease 2
c.953-7C>A Single submitter aortic valve disease 2
c.-15G>C Single submitter
p.Ala149= Single submitter Inborn genetic diseases
p.Ala153= Single submitter aortic valve disease 2
p.Ala161= Single submitter Inborn genetic diseases
p.Ala194= Single submitter Inborn genetic diseases
p.Ala211= Single submitter aortic valve disease 2
p.Ala252= Single submitter Inborn genetic diseases
p.Ala449Gly Single submitter Inborn genetic diseases
p.Ala98= Single submitter Inborn genetic diseases
p.Arg132= Single submitter aortic valve disease 2
p.Arg139= Single submitter Inborn genetic diseases
p.Arg139Pro Single submitter
p.Arg157= Single submitter aortic valve disease 2
p.Arg159= Single submitter aortic valve disease 2
p.Arg17= Single submitter aortic valve disease 2
p.Arg186= Single submitter aortic valve disease 2
p.Arg268= Single submitter Inborn genetic diseases
p.Arg281= Single submitter Inborn genetic diseases
p.Arg3= Single submitter aortic valve disease 2
p.Arg342= Single submitter Inborn genetic diseases
p.Arg405= Single submitter aortic valve disease 2
p.Arg423= Single submitter aortic valve disease 2
p.Arg57= Single submitter Inborn genetic diseases
p.Arg6= Single submitter aortic valve disease 2
p.Arg82= Single submitter Inborn genetic diseases
p.Arg83= Single submitter aortic valve disease 2
p.Asp140= Single submitter Inborn genetic diseases
p.Asp324= Single submitter Inborn genetic diseases
p.Asp351= Single submitter aortic valve disease 2
p.Asp418= Single submitter aortic valve disease 2
p.Cys270= Single submitter aortic valve disease 2
p.Gln218= Single submitter aortic valve disease 2
p.Gln78= Single submitter Inborn genetic diseases
p.Glu118= Single submitter Inborn genetic diseases
p.Glu151= Single submitter Inborn genetic diseases
p.Glu171= Single submitter aortic valve disease 2
p.Glu185= Single submitter aortic valve disease 2
p.Glu193= Single submitter Inborn genetic diseases
p.Glu287= Single submitter aortic valve disease 2
p.Glu302= Single submitter aortic valve disease 2
p.Glu407= Single submitter aortic valve disease 2
p.Glu489= Single submitter aortic valve disease 2
p.Glu51= Single submitter aortic valve disease 2
p.Gly101= Single submitter Inborn genetic diseases
p.Gly136= Single submitter Inborn genetic diseases
p.Gly155= Single submitter aortic valve disease 2
p.Gly200= Single submitter Inborn genetic diseases
p.Gly216= Single submitter Inborn genetic diseases
p.Gly227= Single submitter Inborn genetic diseases
p.Gly256= Single submitter aortic valve disease 2
p.Gly26= Single submitter Inborn genetic diseases
p.Gly29= Single submitter Inborn genetic diseases
p.Gly31= Single submitter aortic valve disease 2
p.Gly33= Single submitter aortic valve disease 2
p.Gly344= Single submitter aortic valve disease 2
p.Gly422= Single submitter Inborn genetic diseases
p.Gly433= Single submitter aortic valve disease 2
p.Gly457= Single submitter aortic valve disease 2
p.Gly52= Single submitter Inborn genetic diseases
p.Gly56= Single submitter aortic valve disease 2
p.Gly79= Single submitter Inborn genetic diseases
p.Gly81= Single submitter
p.Gly88= Single submitter aortic valve disease 2
p.Gly97= Single submitter aortic valve disease 2
p.His339= Single submitter Inborn genetic diseases
p.His448= Single submitter aortic valve disease 2
p.Leu104Pro Single submitter Inborn genetic diseases
p.Leu116= Single submitter Inborn genetic diseases
p.Leu145= Single submitter Inborn genetic diseases
p.Leu168= Single submitter aortic valve disease 2
p.Leu172= Single submitter aortic valve disease 2
p.Leu179= Single submitter Inborn genetic diseases
p.Leu192= Single submitter aortic valve disease 2
p.Leu225= Single submitter Inborn genetic diseases
p.Leu226= Single submitter aortic valve disease 2
p.Leu360= Single submitter Inborn genetic diseases
p.Leu373= Single submitter aortic valve disease 2
p.Leu446= Single submitter Inborn genetic diseases
p.Leu488= Single submitter Inborn genetic diseases
p.Leu491= Single submitter Inborn genetic diseases
p.Lys173= Single submitter Inborn genetic diseases
p.Lys181= Single submitter Inborn genetic diseases
p.Lys289= Single submitter Inborn genetic diseases
p.Lys327= Single submitter Inborn genetic diseases
p.Lys386= Single submitter aortic valve disease 2
p.Lys437= Single submitter aortic valve disease 2
p.Phe230= Single submitter Inborn genetic diseases
p.Phe250= Single submitter aortic valve disease 2
p.Phe366= Single submitter aortic valve disease 2
p.Pro110= Single submitter aortic valve disease 2
p.Pro113= Single submitter Inborn genetic diseases
p.Pro117= Single submitter aortic valve disease 2
p.Pro144= Single submitter aortic valve disease 2
p.Pro152= Single submitter Inborn genetic diseases
p.Pro219= Single submitter Inborn genetic diseases
p.Pro221= Single submitter Inborn genetic diseases
p.Pro222= Single submitter Inborn genetic diseases
p.Pro243= Single submitter aortic valve disease 2
p.Pro257= Single submitter Inborn genetic diseases
p.Pro313= Single submitter Inborn genetic diseases
p.Pro415= Single submitter aortic valve disease 2
p.Pro431= Single submitter Inborn genetic diseases
p.Pro495His Single submitter Inborn genetic diseases
p.Pro62= Single submitter Inborn genetic diseases
p.Ser102Gly Single submitter Inborn genetic diseases
p.Ser130= Single submitter aortic valve disease 2
p.Ser142Gly Single submitter Inborn genetic diseases
p.Ser163= Single submitter Inborn genetic diseases
p.Ser178= Single submitter Inborn genetic diseases
p.Ser333= Single submitter Inborn genetic diseases
p.Ser385= Single submitter aortic valve disease 2
p.Ser4= Single submitter aortic valve disease 2
p.Ser414= Single submitter aortic valve disease 2
p.Ser435= Single submitter Inborn genetic diseases
p.Ser444= Single submitter Inborn genetic diseases
p.Ser463= Single submitter aortic valve disease 2
p.Ser467= Single submitter aortic valve disease 2
p.Ser483= Single submitter aortic valve disease 2
p.Ter497= Single submitter aortic valve disease 2
p.Thr174= Single submitter Inborn genetic diseases
p.Thr258= Single submitter Inborn genetic diseases
p.Thr482= Single submitter
p.Tyr264= Single submitter Inborn genetic diseases
p.Tyr300= Single submitter aortic valve disease 2
p.Tyr336= Single submitter Inborn genetic diseases
p.Tyr347= Single submitter Inborn genetic diseases
p.Tyr350= Single submitter aortic valve disease 2
p.Tyr476= Single submitter aortic valve disease 2
p.Val107= Single submitter aortic valve disease 2
p.Val175= Single submitter Inborn genetic diseases
p.Val426= Single submitter aortic valve disease 2
p.Val427= Single submitter Inborn genetic diseases
p.Val430= Single submitter Inborn genetic diseases
c.953-9G>A No assertion criteria SMAD6-related disease
p.Ala71= No assertion criteria SMAD6-related disease
p.Arg66= No assertion criteria SMAD6-related disease
p.Cys121= No assertion criteria SMAD6-related disease

Uncertain significance 794

Showing the top 300 by review status; the full set is in the sitemap.

c.806_817+19del Multiple submitters aortic valve disease 2
c.817+4A>G Multiple submitters aortic valve disease 2
p.Ala100Pro Multiple submitters Inborn genetic diseases ⚠
p.Ala100Thr Multiple submitters Inborn genetic diseases ⚠
p.Ala134Thr Multiple submitters Inborn genetic diseases ⚠
p.Ala135Thr Multiple submitters Inborn genetic diseases ⚠
p.Ala161Ser Multiple submitters aortic valve disease 2 ⚠
p.Ala211Gly Multiple submitters aortic valve disease 2 ⚠
p.Ala211Val Multiple submitters Inborn genetic diseases ⚠
p.Ala253Thr Multiple submitters Inborn genetic diseases ⚠
p.Ala254dup Multiple submitters aortic valve disease 2
p.Ala353fs Multiple submitters aortic valve disease 2
p.Ala424Val Multiple submitters Inborn genetic diseases ⚠
p.Ala449Val Multiple submitters Inborn genetic diseases ⚠
p.Ala454Pro Multiple submitters aortic valve disease 2 ⚠
p.Ala455Thr Multiple submitters aortic valve disease 2 ⚠
p.Ala469Pro Multiple submitters aortic valve disease 2 ⚠
p.Ala80Val Multiple submitters aortic valve disease 2 ⚠
p.Ala86Val Multiple submitters Inborn genetic diseases ⚠
p.Arg11Gln Multiple submitters aortic valve disease 2 ⚠
p.Arg12Gln Multiple submitters Inborn genetic diseases ⚠
p.Arg132Leu Multiple submitters Inborn genetic diseases ⚠
p.Arg139Trp Multiple submitters Inborn genetic diseases ⚠
p.Arg157Trp Multiple submitters aortic valve disease 2 ⚠
p.Arg15Gly Multiple submitters aortic valve disease 2 ⚠
p.Arg162Cys Multiple submitters aortic valve disease 2
p.Arg164Trp Multiple submitters Inborn genetic diseases
p.Arg17His Multiple submitters Inborn genetic diseases ⚠
p.Arg182Trp Multiple submitters Inborn genetic diseases ⚠
p.Arg186Cys Multiple submitters Inborn genetic diseases
p.Arg186Pro Multiple submitters Inborn genetic diseases
p.Arg198Gly Multiple submitters aortic valve disease 2 ⚠
p.Arg210Cys Multiple submitters aortic valve disease 2 ⚠
p.Arg214His Multiple submitters aortic valve disease 2 ⚠
p.Arg228Pro Multiple submitters Inborn genetic diseases ⚠
p.Arg231Cys Multiple submitters Inborn genetic diseases ⚠
p.Arg268Trp Multiple submitters aortic valve disease 2 ⚠
p.Arg281Gln Multiple submitters aortic valve disease 2 ⚠
p.Arg281Trp Multiple submitters Inborn genetic diseases ⚠
p.Arg3Lys Multiple submitters Inborn genetic diseases ⚠
p.Arg428Cys Multiple submitters aortic valve disease 2 ⚠
p.Arg428His Multiple submitters aortic valve disease 2 ⚠
p.Arg42Gln Multiple submitters aortic valve disease 2 ⚠
p.Arg443Pro Multiple submitters Inborn genetic diseases ⚠
p.Arg465Cys Multiple submitters aortic valve disease 2 ⚠
p.Arg478Gln Multiple submitters Inborn genetic diseases ⚠
p.Arg6Cys Multiple submitters aortic valve disease 2 ⚠
p.Arg82Lys Multiple submitters Inborn genetic diseases ⚠
p.Arg83Gly Multiple submitters aortic valve disease 2 ⚠
p.Arg84Leu Multiple submitters Inborn genetic diseases ⚠
p.Arg84Trp Multiple submitters aortic valve disease 2 ⚠
p.Arg91fs Multiple submitters aortic valve disease 2
p.Arg91Met Multiple submitters aortic valve disease 2 ⚠
p.Asn307Lys Multiple submitters aortic valve disease 2
p.Asn404Ser Multiple submitters Inborn genetic diseases ⚠
p.Asn462Ser Multiple submitters aortic valve disease 2 ⚠
p.Asp106Asn Multiple submitters aortic valve disease 2 ⚠
p.Asp143Glu Multiple submitters Inborn genetic diseases ⚠
p.Asp212Gly Multiple submitters aortic valve disease 2 ⚠
p.Asp255Ala Multiple submitters Inborn genetic diseases ⚠
p.Asp286Asn Multiple submitters Inborn genetic diseases ⚠
p.Asp286Gly Multiple submitters Inborn genetic diseases ⚠
p.Asp292Asn Multiple submitters aortic valve disease 2 ⚠
p.Asp295_Ser296del Multiple submitters aortic valve disease 2
p.Asp295Asn Multiple submitters Inborn genetic diseases
p.Asp359His Multiple submitters aortic valve disease 2 ⚠
p.Asp36Gly Multiple submitters aortic valve disease 2 ⚠
p.Asp36Tyr Multiple submitters Inborn genetic diseases ⚠
p.Asp36Val Multiple submitters Inborn genetic diseases ⚠
p.Asp440Asn Multiple submitters Inborn genetic diseases ⚠
p.Asp70Glu Multiple submitters Inborn genetic diseases ⚠
p.Asp70Val Multiple submitters aortic valve disease 2 ⚠
p.Cys205Gly Multiple submitters aortic valve disease 2 ⚠
p.Cys261Gly Multiple submitters Inborn genetic diseases ⚠
p.Cys261Tyr Multiple submitters Inborn genetic diseases ⚠
p.Cys484Tyr Multiple submitters Inborn genetic diseases ⚠
p.Gln362Arg Multiple submitters Inborn genetic diseases ⚠
p.Gln74His Multiple submitters aortic valve disease 2 ⚠
p.Glu118Lys Multiple submitters Inborn genetic diseases ⚠
p.Glu118Ter Multiple submitters aortic valve disease 2
p.Glu151Asp Multiple submitters aortic valve disease 2 ⚠
p.Glu185Lys Multiple submitters aortic valve disease 2 ⚠
p.Glu24Gly Multiple submitters Inborn genetic diseases ⚠
p.Glu35Gly Multiple submitters Inborn genetic diseases ⚠
p.Glu378Lys Multiple submitters Inborn genetic diseases
p.Glu489Lys Multiple submitters aortic valve disease 2 ⚠
p.Glu51Asp Multiple submitters aortic valve disease 2 ⚠
p.Gly111Glu Multiple submitters aortic valve disease 2 ⚠
p.Gly147Arg Multiple submitters Inborn genetic diseases ⚠
p.Gly155Cys Multiple submitters Inborn genetic diseases ⚠
p.Gly156Arg Multiple submitters aortic valve disease 2 ⚠
p.Gly156Trp Multiple submitters Inborn genetic diseases ⚠
p.Gly200Ser Multiple submitters Inborn genetic diseases ⚠
p.Gly203Arg Multiple submitters Inborn genetic diseases ⚠
p.Gly204Ser Multiple submitters aortic valve disease 2 ⚠
p.Gly28Ser Multiple submitters aortic valve disease 2 ⚠
p.Gly31Ser Multiple submitters Inborn genetic diseases ⚠
p.Gly33Cys Multiple submitters Inborn genetic diseases ⚠
p.Gly471Val Multiple submitters aortic valve disease 2 ⚠
p.Gly81Glu Multiple submitters Inborn genetic diseases ⚠
p.Gly87Trp Multiple submitters aortic valve disease 2 ⚠
p.Gly88Cys Multiple submitters aortic valve disease 2 ⚠
p.Gly99Ser Multiple submitters Inborn genetic diseases ⚠
p.His265Arg Multiple submitters Inborn genetic diseases ⚠
p.His265Tyr Multiple submitters aortic valve disease 2 ⚠
p.His408Gln Multiple submitters aortic valve disease 2 ⚠
p.Ile310Val Multiple submitters aortic valve disease 2 ⚠
p.Ile356Val Multiple submitters aortic valve disease 2 ⚠
p.Ile410Val Multiple submitters Inborn genetic diseases ⚠
p.Leu116Val Multiple submitters Inborn genetic diseases ⚠
p.Leu13Phe Multiple submitters Inborn genetic diseases ⚠
p.Leu145Pro Multiple submitters aortic valve disease 2 ⚠
p.Leu226Phe Multiple submitters Inborn genetic diseases ⚠
p.Leu229Val Multiple submitters SMAD6-related disease ⚠
p.Leu244Pro Multiple submitters aortic valve disease 2 ⚠
p.Leu244Val Multiple submitters Inborn genetic diseases ⚠
p.Leu269Val Multiple submitters Inborn genetic diseases ⚠
p.Leu291Pro Multiple submitters aortic valve disease 2
p.Leu368Val Multiple submitters Inborn genetic diseases ⚠
p.Leu373Pro Multiple submitters Inborn genetic diseases ⚠
p.Leu392Pro Multiple submitters Inborn genetic diseases ⚠
p.Leu393Pro Multiple submitters aortic valve disease 2 ⚠
p.Leu9Val Multiple submitters Inborn genetic diseases ⚠
p.Met1Arg Multiple submitters aortic valve disease 2
p.Met321Leu Multiple submitters aortic valve disease 2 ⚠
p.Met93Ile Multiple submitters aortic valve disease 2 ⚠
p.Met93Leu Multiple submitters aortic valve disease 2 ⚠
p.Met93Thr Multiple submitters aortic valve disease 2 ⚠
p.Pro110Ser Multiple submitters aortic valve disease 2 ⚠
p.Pro117Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro138Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro144Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro144Thr Multiple submitters aortic valve disease 2 ⚠
p.Pro202Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro222Arg Multiple submitters Inborn genetic diseases ⚠
p.Pro222Gln Multiple submitters Inborn genetic diseases ⚠
p.Pro233Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro243Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro263Ser Multiple submitters aortic valve disease 2 ⚠
p.Pro272Ala Multiple submitters aortic valve disease 2 ⚠
p.Pro272Ser Multiple submitters Inborn genetic diseases
p.Pro278Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro278Ser Multiple submitters Inborn genetic diseases ⚠
p.Pro284Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro313Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro323Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro328Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro397His Multiple submitters Inborn genetic diseases ⚠
p.Pro397Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro409Ser Multiple submitters aortic valve disease 2 ⚠
p.Pro415Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro431His Multiple submitters Inborn genetic diseases
p.Pro432Ala Multiple submitters Inborn genetic diseases ⚠
p.Pro450Ser Multiple submitters Inborn genetic diseases ⚠
p.Pro450Thr Multiple submitters aortic valve disease 2 ⚠
p.Pro452Arg Multiple submitters aortic valve disease 2 ⚠
p.Pro45Arg Multiple submitters Inborn genetic diseases ⚠
p.Pro461Ser Multiple submitters Inborn genetic diseases ⚠
p.Pro474fs Multiple submitters craniosynostosis 7
p.Pro62Ser Multiple submitters Inborn genetic diseases ⚠
p.Pro65Leu Multiple submitters Inborn genetic diseases ⚠
p.Pro68Ser Multiple submitters Inborn genetic diseases ⚠
p.Pro89Leu Multiple submitters aortic valve disease 2 ⚠
p.Pro90fs Multiple submitters craniosynostosis 7
p.Pro90Ser Multiple submitters Inborn genetic diseases ⚠
p.Ser130Pro Multiple submitters Inborn genetic diseases ⚠
p.Ser158Arg Multiple submitters aortic valve disease 2 ⚠
p.Ser158Gly Multiple submitters aortic valve disease 2 ⚠
p.Ser163Leu Multiple submitters Inborn genetic diseases ⚠
p.Ser16Asn Multiple submitters Inborn genetic diseases ⚠
p.Ser178Trp Multiple submitters Inborn genetic diseases ⚠
p.Ser267Arg Multiple submitters aortic valve disease 2 ⚠
p.Ser27_Gly29del Multiple submitters craniosynostosis 7
p.Ser27Asn Multiple submitters Inborn genetic diseases ⚠
p.Ser333Asn Multiple submitters aortic valve disease 2 ⚠
p.Ser444Leu Multiple submitters Inborn genetic diseases ⚠
p.Ser483Phe Multiple submitters Inborn genetic diseases ⚠
p.Ser58Pro Multiple submitters Inborn genetic diseases ⚠
p.Thr303Met Multiple submitters aortic valve disease 2 ⚠
p.Thr326Ala Multiple submitters Inborn genetic diseases ⚠
p.Thr341Met Multiple submitters aortic valve disease 2 ⚠
p.Thr383Met Multiple submitters aortic valve disease 2 ⚠
p.Thr482Ser Multiple submitters aortic valve disease 2 ⚠
p.Tyr336His Multiple submitters SMAD6-related disease ⚠
p.Tyr434His Multiple submitters aortic valve disease 2 ⚠
p.Val18Gly Multiple submitters Inborn genetic diseases ⚠
p.Val195Met Multiple submitters Inborn genetic diseases ⚠
p.Val19Phe Multiple submitters Inborn genetic diseases ⚠
p.Val208Ala Multiple submitters Inborn genetic diseases
p.Val259Leu Multiple submitters Inborn genetic diseases ⚠
p.Val400Leu Multiple submitters Inborn genetic diseases ⚠
p.Val400Met Multiple submitters Inborn genetic diseases ⚠
p.Val426Ile Multiple submitters Inborn genetic diseases ⚠
p.Val60Ile Multiple submitters aortic valve disease 2 ⚠
c.817+1G>T Single submitter
c.817+3G>T Single submitter
c.817+5G>C Single submitter aortic valve disease 2
c.818-2del Single submitter aortic valve disease 2
c.874+1G>C Single submitter aortic valve disease 2
c.874+4A>C Single submitter aortic valve disease 2
c.875-1G>A Single submitter aortic valve disease 2
c.875-1G>C Single submitter aortic valve disease 2
c.875-1G>T Single submitter aortic valve disease 2
c.875-2A>T Single submitter aortic valve disease 2
c.953-2_968del Single submitter aortic valve disease 2
c.953-2A>G Single submitter aortic valve disease 2
p.Ala100Ser Single submitter Inborn genetic diseases ⚠
p.Ala100Val Single submitter aortic valve disease 2 ⚠
p.Ala108Gly Single submitter Inborn genetic diseases ⚠
p.Ala108Ter Single submitter aortic valve disease 2
p.Ala108Val Single submitter aortic valve disease 2 ⚠
p.Ala134Val Single submitter ⚠
p.Ala135Ser Single submitter Inborn genetic diseases ⚠
p.Ala141_Ser142insAlaGlyAlaProArgAspAla Single submitter aortic valve disease 2
p.Ala141Gly Single submitter aortic valve disease 2 ⚠
p.Ala146_Leu150del Single submitter aortic valve disease 2
p.Ala146Val Single submitter Inborn genetic diseases ⚠
p.Ala148Val Single submitter Inborn genetic diseases ⚠
p.Ala149Val Single submitter aortic valve disease 2 ⚠
p.Ala153Glu Single submitter Inborn genetic diseases ⚠
p.Ala153Gly Single submitter Inborn genetic diseases ⚠
p.Ala153Thr Single submitter Inborn genetic diseases ⚠
p.Ala211_Asp212insCysValLeuValProArgAla Single submitter aortic valve disease 2
p.Ala220Val Single submitter ⚠
p.Ala251Gly Single submitter aortic valve disease 2 ⚠
p.Ala252Ser Single submitter aortic valve disease 2 ⚠
p.Ala254_Asp255insAlaAla Single submitter
p.Ala254Gly Single submitter Inborn genetic diseases ⚠
p.Ala319Thr Single submitter ⚠
p.Ala325fs Single submitter aortic valve disease 2
p.Ala335Glu Single submitter aortic valve disease 2 ⚠
p.Ala335Val Single submitter aortic valve disease 2 ⚠
p.Ala348fs Single submitter aortic valve disease 2
p.Ala353Thr Single submitter aortic valve disease 2 ⚠
p.Ala419Thr Single submitter aortic valve disease 2 ⚠
p.Ala43Pro Single submitter aortic valve disease 2 ⚠
p.Ala449Thr Single submitter Inborn genetic diseases ⚠
p.Ala454Thr Single submitter aortic valve disease 2 ⚠
p.Ala469Thr Single submitter Inborn genetic diseases ⚠
p.Ala46Val Single submitter aortic valve disease 2 ⚠
p.Ala49Gly Single submitter aortic valve disease 2 ⚠
p.Ala49Pro Single submitter Inborn genetic diseases ⚠
p.Ala64Ser Single submitter aortic valve disease 2 ⚠
p.Ala71Val Single submitter aortic valve disease 2 ⚠
p.Ala77Thr Single submitter Inborn genetic diseases ⚠
p.Ala77Val Single submitter Inborn genetic diseases ⚠
p.Ala80Gly Single submitter ⚠
p.Ala86Ser Single submitter Inborn genetic diseases ⚠
p.Ala98Ser Single submitter aortic valve disease 2 ⚠
p.Ala98Val Single submitter aortic valve disease 2 ⚠
p.Arg11Gly Single submitter Inborn genetic diseases ⚠
p.Arg11Pro Single submitter congenital anomaly of kidney and urinary tract ⚠
p.Arg11Trp Single submitter aortic valve disease 2 ⚠
p.Arg132Gly Single submitter aortic valve disease 2 ⚠
p.Arg139Gly Single submitter Inborn genetic diseases ⚠
p.Arg159Gly Single submitter aortic valve disease 2 ⚠
p.Arg162Leu Single submitter aortic valve disease 2 ⚠
p.Arg162Pro Single submitter aortic valve disease 2 ⚠
p.Arg162Ser Single submitter Inborn genetic diseases ⚠
p.Arg164_Leu165insArg Single submitter aortic valve disease 2
p.Arg17Cys Single submitter aortic valve disease 2 ⚠
p.Arg17Ser Single submitter Inborn genetic diseases ⚠
p.Arg186His Single submitter aortic valve disease 2 ⚠
p.Arg198Cys Single submitter aortic valve disease 2 ⚠
p.Arg198Pro Single submitter Inborn genetic diseases ⚠
p.Arg214Cys Single submitter Inborn genetic diseases ⚠
p.Arg214fs Single submitter aortic valve disease 2
p.Arg214Gly Single submitter Inborn genetic diseases ⚠
p.Arg214Leu Single submitter aortic valve disease 2 ⚠
p.Arg228Cys Single submitter Inborn genetic diseases ⚠
p.Arg228Gly Single submitter aortic valve disease 2 ⚠
p.Arg228His Single submitter aortic valve disease 2 ⚠
p.Arg228Leu Single submitter aortic valve disease 2
p.Arg228Ser Single submitter ⚠
p.Arg22Gln Single submitter Inborn genetic diseases ⚠
p.Arg22Pro Single submitter ⚠
p.Arg22Trp Single submitter aortic valve disease 2 ⚠
p.Arg231Gly Single submitter aortic valve disease 2 ⚠
p.Arg231Leu Single submitter Inborn genetic diseases ⚠
p.Arg231Ser Single submitter aortic valve disease 2 ⚠
p.Arg268Gln Single submitter Inborn genetic diseases ⚠
p.Arg281Leu Single submitter Inborn genetic diseases ⚠
p.Arg285Pro Single submitter Inborn genetic diseases ⚠
p.Arg342Cys Single submitter aortic valve disease 2 ⚠
p.Arg342His Single submitter aortic valve disease 2 ⚠
p.Arg342Pro Single submitter aortic valve disease 2 ⚠
p.Arg376His Single submitter aortic valve disease 2 ⚠
p.Arg381Gly Single submitter aortic valve disease 2 ⚠
p.Arg381Pro Single submitter Inborn genetic diseases ⚠
p.Arg382Leu Single submitter aortic valve disease 2 ⚠
p.Arg382Pro Single submitter Inborn genetic diseases ⚠
p.Arg3Ser Single submitter Inborn genetic diseases ⚠
p.Arg405Gly Single submitter Inborn genetic diseases ⚠
p.Arg405His Single submitter Inborn genetic diseases ⚠
p.Arg423His Single submitter Inborn genetic diseases ⚠
p.Arg42Pro Single submitter Inborn genetic diseases ⚠
p.Arg443Cys Single submitter aortic valve disease 2 ⚠
p.Arg443Leu Single submitter Inborn genetic diseases ⚠
p.Arg478Gly Single submitter Inborn genetic diseases ⚠
p.Arg48Trp Single submitter aortic valve disease 2 ⚠