SIX6 — 155 ClinVar variants
All ClinVar germline SIX6 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 66 flagged for review →
3 Pathogenic · 5 Likely pathogenic · 7 Conflicting · 5 Benign · 1 Benign/Likely benign · 52 Likely benign · 82 Uncertain significance
Full SIX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 66
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 agree, ClinVar conflicts 4
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
SIX6 p.Glu129Lys
Conflicting
Single submitter
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
-
SIX6 p.Leu205Arg
Conflicting
Single submitter
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- SIX6 p.Lys158Thr Conflicting Single submitter
-
SIX6 p.Pro213Ser
Conflicting
Single submitter
Anophthalmia-microphthalmia syndrome
Predictors lean, ClinVar uncertain 48
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
SIX6 p.Gln130Arg
Uncertain significance
Multiple submitters
Anophthalmia-microphthalmia syndrome
- SIX6 p.Gln193His Uncertain significance Multiple submitters
- SIX6 p.Glu45Asp Uncertain significance Multiple submitters
- SIX6 p.Lys136Thr Uncertain significance Multiple submitters
- SIX6 p.Ala224Val Uncertain significance Single submitter
- SIX6 p.Ala230Glu Uncertain significance Single submitter
- SIX6 p.Ala231Thr Uncertain significance Single submitter
- SIX6 p.Ala42Thr Uncertain significance Single submitter
- SIX6 p.Ala46Thr Uncertain significance Single submitter
- SIX6 p.Arg103Leu Uncertain significance Single submitter
- SIX6 p.Arg105Thr Uncertain significance Single submitter
- SIX6 p.Arg116Lys Uncertain significance Single submitter
- SIX6 p.Arg140Gly Uncertain significance Single submitter
- SIX6 p.Arg159His Uncertain significance Single submitter
- SIX6 p.Arg159Ser Uncertain significance Single submitter
- SIX6 p.Arg184Gly Uncertain significance Single submitter
- SIX6 p.Arg203Gln Uncertain significance Single submitter
-
SIX6 p.Arg203Trp
Uncertain significance
Single submitter
Anophthalmia-microphthalmia syndrome
- SIX6 p.Arg206Gly Uncertain significance Single submitter
- SIX6 p.Arg57Pro Uncertain significance Single submitter
- SIX6 p.Asn174Ser Uncertain significance Single submitter
- SIX6 p.Asn178Thr Uncertain significance Single submitter
- SIX6 p.Asn48Ser Uncertain significance Single submitter
- SIX6 p.Glu137Ala Uncertain significance Single submitter
- SIX6 p.Glu19Lys Uncertain significance Single submitter
- SIX6 p.Glu208Lys Uncertain significance Single submitter
- SIX6 p.Glu22Val Uncertain significance Single submitter
- SIX6 p.Glu243Lys Uncertain significance Single submitter
-
SIX6 p.Gly166Arg
Uncertain significance
Single submitter
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- SIX6 p.Gly209Cys Uncertain significance Single submitter
- SIX6 p.Gly31Arg Uncertain significance Single submitter
- SIX6 p.His72Gln Uncertain significance Single submitter
- SIX6 p.Leu148Arg Uncertain significance Single submitter
- SIX6 p.Leu30Val Uncertain significance Single submitter
- SIX6 p.Phe62Cys Uncertain significance Single submitter
- SIX6 p.Pro106Arg Uncertain significance Single submitter
- SIX6 p.Pro41Arg Uncertain significance Single submitter
-
SIX6 p.Ser242Ile
Uncertain significance
Single submitter
Anophthalmia-microphthalmia syndrome
- SIX6 p.Ser52Trp Uncertain significance Single submitter
- SIX6 p.Thr132Ala Uncertain significance Single submitter
- SIX6 p.Thr168Ile Uncertain significance Single submitter
- SIX6 p.Thr232Ile Uncertain significance Single submitter
- SIX6 p.Thr80Asn Uncertain significance Single submitter
- SIX6 p.Trp126Arg Uncertain significance Single submitter
-
SIX6 p.Val110Leu
Uncertain significance
Single submitter
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- SIX6 p.Val172Ala Uncertain significance Single submitter
- SIX6 p.Val218Ile Uncertain significance Single submitter
- SIX6 p.Val218Phe Uncertain significance Single submitter
Predictors split 14
The independent predictors disagree with each other — read with care.
- SIX6 p.Ala89Thr Uncertain significance Multiple submitters
-
SIX6 p.Thr212Met
Uncertain significance
Multiple submitters
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- SIX6 p.Asp26Asn Uncertain significance Single submitter
- SIX6 p.Cys244Arg Uncertain significance Single submitter
- SIX6 p.Cys244Tyr Uncertain significance Single submitter
- SIX6 p.Gln12Lys Uncertain significance Single submitter
- SIX6 p.Ile237Thr Uncertain significance Single submitter
- SIX6 p.Leu4Met Uncertain significance Single submitter
- SIX6 p.Lys49Glu Uncertain significance Single submitter
- SIX6 p.Pro41Ser Uncertain significance Single submitter
- SIX6 p.Ser10Gly Uncertain significance Single submitter
- SIX6 p.Ser221Cys Uncertain significance Single submitter
- SIX6 p.Val60Leu Uncertain significance Single submitter
-
SIX6 p.Thr165Ala
Uncertain significance
No assertion criteria
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
All SIX6 variants
Pathogenic 3
- c.-227_572+235del Single submitter microphthalmia
- p.Asp183His Single submitter pathologic nystagmus
- p.Leu37Pro No assertion criteria colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
Likely pathogenic 5
- p.Asn178fs Multiple submitters colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- p.Asp127fs Single submitter
- p.Asp183Glu Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- p.Glu145Ter Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
- p.Trp35Ter Single submitter
Conflicting classifications of pathogenicity 7
- c.572+15G>A Single submitter Anophthalmia-microphthalmia syndrome
- c.573-6C>G Single submitter Anophthalmia-microphthalmia syndrome
- p.Glu129Lys Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠
- p.Gly217= Single submitter Anophthalmia-microphthalmia syndrome
- p.Leu205Arg Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠
- p.Lys158Thr Single submitter ⚠
- p.Pro213Ser Single submitter Anophthalmia-microphthalmia syndrome ⚠
Benign 5
- c.-161T>C Multiple submitters Anophthalmia-microphthalmia syndrome
- c.*101C>G Multiple submitters Anophthalmia-microphthalmia syndrome
- p.His141Asn Multiple submitters Anophthalmia-microphthalmia syndrome
- c.573-184G>A Single submitter
- p.Ile6= Single submitter
Benign/Likely benign 1
- p.Leu7= Multiple submitters Anophthalmia-microphthalmia syndrome
Likely benign 52
- c.-147T>C Multiple submitters Anophthalmia-microphthalmia syndrome
- c.-64C>T Multiple submitters Anophthalmia-microphthalmia syndrome
- p.Ala58= Multiple submitters
- c.572+10T>C Single submitter
- c.572+13A>G Single submitter
- c.572+20C>T Single submitter
- c.572+8C>T Single submitter
- c.573-10T>C Single submitter
- c.573-5C>G Single submitter
- c.-149C>T Single submitter Anophthalmia-microphthalmia syndrome
- p.Ala207= Single submitter
- p.Ala61= Single submitter
- p.Ala89= Single submitter
- p.Arg123= Single submitter
- p.Arg144= Single submitter
- p.Arg206= Single submitter
- p.Arg57= Single submitter
- p.Asn174= Single submitter
- p.Asn178= Single submitter
- p.Asn48= Single submitter
- p.Asp111= Single submitter
- p.Asp26= Single submitter
- p.Gln163= Single submitter
- p.Glu100= Single submitter
- p.Glu145= Single submitter
- p.Glu208= Single submitter
- p.Glu93= Single submitter
- p.Glu98= Single submitter
- p.Gly209= Single submitter
- p.Gly25= Single submitter
- p.His133= Single submitter
- p.His72= Single submitter
- p.His84= Single submitter
- p.Ile235= Single submitter
- p.Ile246Asn Single submitter
- p.Leu143= Single submitter
- p.Leu197= Single submitter
- p.Leu30= Single submitter
- p.Leu37= Single submitter
- p.Leu4= Single submitter
- p.Leu54= Single submitter
- p.Leu87= Single submitter
- p.Lys81= Single submitter
- p.Pro109= Single submitter
- p.Pro169= Single submitter
- p.Pro38= Single submitter
- p.Pro41= Single submitter
- p.Ser201= Single submitter
- p.Thr212= Single submitter
- p.Val172= Single submitter
- p.Val218= Single submitter
- p.Val39= Single submitter
Uncertain significance 82
- p.Ala89Thr Multiple submitters ⚠
- p.Gln130Arg Multiple submitters Anophthalmia-microphthalmia syndrome ⚠
- p.Gln193His Multiple submitters ⚠
- p.Glu45Asp Multiple submitters ⚠
- p.Lys136Thr Multiple submitters ⚠
- p.Thr212Met Multiple submitters colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠
- p.Ser242Ile Single submitter
- c.-114G>A Single submitter Anophthalmia-microphthalmia syndrome
- c.-174C>G Single submitter Anophthalmia-microphthalmia syndrome
- c.*121A>T Single submitter Anophthalmia-microphthalmia syndrome
- c.*124C>A Single submitter Anophthalmia-microphthalmia syndrome
- c.*210G>T Single submitter Anophthalmia-microphthalmia syndrome
- c.*232C>T Single submitter Anophthalmia-microphthalmia syndrome
- c.*298A>G Single submitter Anophthalmia-microphthalmia syndrome
- c.*409T>G Single submitter Anophthalmia-microphthalmia syndrome
- c.*432G>A Single submitter Anophthalmia-microphthalmia syndrome
- c.*462A>G Single submitter Anophthalmia-microphthalmia syndrome
- p.Ala224Val Single submitter ⚠
- p.Ala230Glu Single submitter ⚠
- p.Ala231Thr Single submitter ⚠
- p.Ala42Thr Single submitter ⚠
- p.Ala46Thr Single submitter ⚠
- p.Arg103Leu Single submitter ⚠
- p.Arg105Thr Single submitter ⚠
- p.Arg114Ter Single submitter
- p.Arg116Lys Single submitter ⚠
- p.Arg140Gly Single submitter ⚠
- p.Arg159His Single submitter ⚠
- p.Arg159Ser Single submitter ⚠
- p.Arg184Gly Single submitter ⚠
- p.Arg203Gln Single submitter ⚠
- p.Arg203Trp Single submitter Anophthalmia-microphthalmia syndrome ⚠
- p.Arg206Gly Single submitter ⚠
- p.Arg32= Single submitter Anophthalmia-microphthalmia syndrome
- p.Arg57Pro Single submitter ⚠
- p.Asn174Ser Single submitter ⚠
- p.Asn178Thr Single submitter ⚠
- p.Asn48Ser Single submitter ⚠
- p.Asp26Asn Single submitter ⚠
- p.Cys244Arg Single submitter ⚠
- p.Cys244Ter Single submitter
- p.Cys244Tyr Single submitter ⚠
- p.Gln12Lys Single submitter ⚠
- p.Gln149Arg Single submitter
- p.Glu137Ala Single submitter ⚠
- p.Glu19Lys Single submitter ⚠
- p.Glu208Lys Single submitter ⚠
- p.Glu22Val Single submitter ⚠
- p.Glu243Lys Single submitter ⚠
- p.Gly166Arg Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠
- p.Gly209Cys Single submitter ⚠
- p.Gly31Arg Single submitter ⚠
- p.His72Gln Single submitter ⚠
- p.Ile237Thr Single submitter ⚠
- p.Leu121fs Single submitter
- p.Leu148Arg Single submitter ⚠
- p.Leu205fs Single submitter
- p.Leu30Val Single submitter ⚠
- p.Leu4Met Single submitter ⚠
- p.Lys49Glu Single submitter ⚠
- p.Lys86fs Single submitter
- p.Phe62Cys Single submitter ⚠
- p.Pro106Arg Single submitter ⚠
- p.Pro41Arg Single submitter ⚠
- p.Pro41Ser Single submitter ⚠
- p.Ser10Gly Single submitter ⚠
- p.Ser221Cys Single submitter ⚠
- p.Ser242= Single submitter Anophthalmia-microphthalmia syndrome
- p.Ser242Ile Single submitter Anophthalmia-microphthalmia syndrome ⚠
- p.Ser52Trp Single submitter ⚠
- p.Thr132Ala Single submitter ⚠
- p.Thr168Ile Single submitter ⚠
- p.Thr232Ile Single submitter ⚠
- p.Thr238= Single submitter Anophthalmia-microphthalmia syndrome
- p.Thr80Asn Single submitter ⚠
- p.Trp126Arg Single submitter ⚠
- p.Val110Leu Single submitter colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠
- p.Val172Ala Single submitter ⚠
- p.Val218Ile Single submitter ⚠
- p.Val218Phe Single submitter ⚠
- p.Val60Leu Single submitter ⚠
- p.Thr165Ala No assertion criteria colobomatous optic disc-macular atrophy-chorioretinopathy syndrome ⚠