CDH15 — 363 ClinVar variants

All ClinVar germline CDH15 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 259 flagged for review →

16 Conflicting · 16 Benign · 4 Benign/Likely benign · 83 Likely benign · 244 Uncertain significance

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 259

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 8

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

CDH15 p.Ala790Val Conflicting Single submitter
intellectual disability, autosomal dominant 3
CDH15 p.Arg36Gln Conflicting Single submitter
CDH15-related disorder
CDH15 p.Glu200Lys Conflicting Single submitter
CDH15 p.Glu206Lys Conflicting Single submitter
CDH15 p.Glu720Ala Conflicting Single submitter
CDH15 p.His435Gln Conflicting Single submitter
CDH15 p.Ile609Met Conflicting Single submitter
CDH15 p.Val54Ile Conflicting Single submitter
intellectual disability

Predictors lean, ClinVar uncertain 116

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 135

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

All CDH15 variants

Conflicting classifications of pathogenicity 16

p.Ala246Val Single submitter neurofibromatosis type 1 ⚠
p.Ala790Val Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg190Trp Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg36Gln Single submitter CDH15-related disorder ⚠
p.Arg44Gln Single submitter ⚠
p.Arg44Trp Single submitter intellectual disability ⚠
p.Asn716Asp Single submitter ⚠
p.Glu200Lys Single submitter ⚠
p.Glu206Lys Single submitter ⚠
p.Glu337Lys Single submitter intellectual disability ⚠
p.Glu720Ala Single submitter ⚠
p.His435Gln Single submitter ⚠
p.Ile609Met Single submitter ⚠
p.Pro705Ser Single submitter ⚠
p.Thr404Ile Single submitter intellectual disability ⚠
p.Val54Ile Single submitter intellectual disability ⚠

Benign 16

p.Ala37Ser Multiple submitters
p.Asp205= Multiple submitters
p.Asp88= Multiple submitters
p.Gln657= Multiple submitters intellectual disability, autosomal dominant 3
p.Leu240Phe Multiple submitters ⚠
p.Lys584Gln Multiple submitters intellectual disability, autosomal dominant 3
p.Pro51= Multiple submitters
p.Pro675= Multiple submitters
p.Ser341= Multiple submitters intellectual disability, autosomal dominant 3
p.Ser470= Multiple submitters
p.Arg556Cys Single submitter ⚠
p.Asp713Asn Single submitter
p.Gly785Arg Single submitter
p.His58= Single submitter
p.Pro685Leu Single submitter
p.Ser77= Single submitter

Benign/Likely benign 4

c.792+7C>T Multiple submitters
p.Gly129= Multiple submitters intellectual disability, autosomal dominant 3
p.His365= Multiple submitters
p.Leu626Phe Multiple submitters ⚠

Likely benign 83

p.Ala122Val Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Ala440= Multiple submitters
p.Arg44= Multiple submitters
p.Arg60Cys Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Arg775Gln Multiple submitters
p.Leu560= Multiple submitters
p.Leu640= Multiple submitters
p.Phe773= Multiple submitters
p.Pro485Leu Multiple submitters
c.1375+10G>A Single submitter
c.1615+3G>A Single submitter
c.1616-6C>T Single submitter
c.1855+9G>A Single submitter
c.1993-5C>G Single submitter
p.Ala108= Single submitter
p.Ala37= Single submitter
p.Ala746Val Single submitter ⚠
p.Arg121= Single submitter
p.Arg160His Single submitter ⚠
p.Arg26= Single submitter
p.Arg297Lys Single submitter ⚠
p.Arg312Leu Single submitter ⚠
p.Arg363= Single submitter
p.Arg400Trp Single submitter
p.Arg463Cys Single submitter ⚠
p.Arg562Gln Single submitter
p.Arg812Gln Single submitter
p.Asn256Ile Single submitter intellectual disability, autosomal dominant 3
p.Asn57= Single submitter
p.Asn576= Single submitter
p.Asp134= Single submitter
p.Asp238= Single submitter
p.Asp742= Single submitter
p.Asp742Glu Single submitter
p.Gln461= Single submitter
p.Glu133= Single submitter
p.Glu183Asp Single submitter
p.Gly275Arg Single submitter ⚠
p.Gly387Ala Single submitter ⚠
p.Gly504= Single submitter
p.Gly583Asp Single submitter ⚠
p.Gly583Ser Single submitter ⚠
p.Gly636= Single submitter
p.Gly659= Single submitter
p.Gly694Ser Single submitter
p.Gly93= Single submitter
p.His641= Single submitter
p.Ile211= Single submitter
p.Ile715= Single submitter
p.Ile97= Single submitter
p.Leu393Pro Single submitter
p.Leu474= Single submitter
p.Leu61= Single submitter
p.Leu672Pro Single submitter intellectual disability, autosomal dominant 3
p.Leu749= Single submitter
p.Lys316Arg Single submitter
p.Pro33= Single submitter
p.Pro373= Single submitter
p.Pro488= Single submitter
p.Pro488_Gly489insPro Single submitter
p.Pro684Leu Single submitter ⚠
p.Pro85= Single submitter
p.Ser460Pro Single submitter
p.Ser55= Single submitter
p.Ser70= Single submitter
p.Thr313Arg Single submitter ⚠
p.Thr313Met Single submitter ⚠
p.Tyr667_Asp668del Single submitter intellectual disability, autosomal dominant 3
p.Tyr763Cys Single submitter intellectual disability ⚠
p.Val104Ala Single submitter
p.Val141= Single submitter
p.Val273Ile Single submitter ⚠
p.Val276= Single submitter
p.Val278= Single submitter
p.Val703Ala Single submitter
c.1376-8G>A No assertion criteria CDH15-related disorder
c.2152-9T>C No assertion criteria CDH15-related disorder
p.Arg812= No assertion criteria CDH15-related disorder
p.Asp663= No assertion criteria CDH15-related disorder
p.Gly660= No assertion criteria CDH15-related disorder
p.His555= No assertion criteria CDH15-related disorder
p.Leu617= No assertion criteria CDH15-related disorder
p.Pro551= No assertion criteria CDH15-related disorder

Uncertain significance 244

c.1232+2T>A Multiple submitters
p.Arg149Trp Multiple submitters ⚠
p.Arg524Ser Multiple submitters ⚠
p.Arg92Trp Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Glu319Lys Multiple submitters von Willebrand disease 1 ⚠
p.Glu472Lys Multiple submitters ⚠
p.Gly514Arg Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Gly599Val Multiple submitters ⚠
p.Gly743Ser Multiple submitters ⚠
p.His513Asn Multiple submitters ⚠
p.Leu528Phe Multiple submitters ⚠
p.Leu805Val Multiple submitters ⚠
p.Pro347Leu Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Pro347Ser Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Pro511Ala Multiple submitters ⚠
p.Ser470Tyr Multiple submitters ⚠
p.Ser744Leu Multiple submitters ⚠
p.Thr158Ala Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Thr184Ser Multiple submitters ⚠
p.Trp34fs Multiple submitters intellectual disability, autosomal dominant 3
p.Tyr739del Multiple submitters intellectual disability, autosomal dominant 3
p.Val43Leu Multiple submitters intellectual disability, autosomal dominant 3 ⚠
p.Val8Leu Multiple submitters ⚠
c.1376-17G>A Single submitter intellectual disability, autosomal dominant 3
c.1615+5G>A Single submitter intellectual disability, autosomal dominant 3
c.*3C>T Single submitter
p.Ala122Pro Single submitter ⚠
p.Ala174Ser Single submitter CDH15-related disorder ⚠
p.Ala188Glu Single submitter ⚠
p.Ala188Val Single submitter ⚠
p.Ala224Val Single submitter ⚠
p.Ala233Val Single submitter ⚠
p.Ala37Val Single submitter ⚠
p.Ala388Thr Single submitter ⚠
p.Ala388Val Single submitter ⚠
p.Ala426Thr Single submitter ⚠
p.Ala484Val Single submitter ⚠
p.Ala597Val Single submitter intellectual disability ⚠
p.Ala612Asp Single submitter ⚠
p.Ala614Thr Single submitter ⚠
p.Ala666Asp Single submitter ⚠
p.Ala666Thr Single submitter ⚠
p.Ala691Gly Single submitter ⚠
p.Ala691Ser Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg112Cys Single submitter ⚠
p.Arg117His Single submitter ⚠
p.Arg121Lys Single submitter ⚠
p.Arg160Cys Single submitter ⚠
p.Arg160Leu Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg173Lys Single submitter ⚠
p.Arg190Gln Single submitter ⚠
p.Arg212Cys Single submitter ⚠
p.Arg220Cys Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg26Lys Single submitter ⚠
p.Arg280Cys Single submitter ⚠
p.Arg286Gly Single submitter ⚠
p.Arg312Cys Single submitter ⚠
p.Arg357Gln Single submitter ⚠
p.Arg35His Single submitter ⚠
p.Arg381Trp Single submitter ⚠
p.Arg42Cys Single submitter ⚠
p.Arg42Leu Single submitter ⚠
p.Arg430Gln Single submitter ⚠
p.Arg430Trp Single submitter ⚠
p.Arg530fs Single submitter
p.Arg571Cys Single submitter ⚠
p.Arg581His Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg581Ser Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg60His Single submitter ⚠
p.Arg635Pro Single submitter ⚠
p.Arg673His Single submitter ⚠
p.Arg688His Single submitter ⚠
p.Arg695Ser Single submitter ⚠
p.Arg702Gln Single submitter ⚠
p.Arg772His Single submitter ⚠
p.Arg812Trp Single submitter ⚠
p.Arg92Gln Single submitter ⚠
p.Arg92Gly Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Arg92Leu Single submitter ⚠
p.Asn107Ser Single submitter ⚠
p.Asn227His Single submitter ⚠
p.Asn344Ile Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Asn531fs Single submitter
p.Asn650Asp Single submitter ⚠
p.Asp126Asn Single submitter ⚠
p.Asp137Tyr Single submitter ⚠
p.Asp178Glu Single submitter ⚠
p.Asp181Asn Single submitter ⚠
p.Asp181Glu Single submitter ⚠
p.Asp263Gly Single submitter ⚠
p.Asp277Glu Single submitter ⚠
p.Asp287Asn Single submitter ⚠
p.Asp417Val Single submitter ⚠
p.Asp420His Single submitter ⚠
p.Asp425Glu Single submitter ⚠
p.Asp509Asn Single submitter ⚠
p.Asp663Glu Single submitter ⚠
p.Asp668Asn Single submitter ⚠
p.Asp723His Single submitter ⚠
p.Asp732Asn Single submitter ⚠
p.Asp742His Single submitter ⚠
p.Asp758Asn Single submitter ⚠
p.Asp758His Single submitter ⚠
p.Asp764Asn Single submitter ⚠
p.Asp778Gly Single submitter ⚠
p.Asp88Asn Single submitter ⚠
p.Gln145His Single submitter ⚠
p.Gln154Arg Single submitter ⚠
p.Gln359Ter Single submitter
p.Gln536Lys Single submitter ⚠
p.Gln536Pro Single submitter ⚠
p.Gln549His Single submitter ⚠
p.Gln644Ter Single submitter
p.Gln671Arg Single submitter ⚠
p.Gln699fs Single submitter intellectual disability, autosomal dominant 3
p.Gln699His Single submitter ⚠
p.Gln699Pro Single submitter ⚠
p.Gln756His Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Gln795His Single submitter ⚠
p.Glu163Gln Single submitter ⚠
p.Glu200Gln Single submitter ⚠
p.Glu210Gln Single submitter ⚠
p.Glu377_Arg381delinsAspLeuTrp Single submitter
p.Glu377Lys Single submitter ⚠
p.Glu572Ter Single submitter
p.Glu656Lys Single submitter ⚠
p.Glu740Gln Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Glu798Asp Single submitter ⚠
p.Gly10Glu Single submitter ⚠
p.Gly307Val Single submitter ⚠
p.Gly320Ala Single submitter ⚠
p.Gly447Asp Single submitter ⚠
p.Gly529Ser Single submitter ⚠
p.Gly591Glu Single submitter ⚠
p.Gly598Ala Single submitter ⚠
p.Gly605Arg Single submitter ⚠
p.Gly636Ser Single submitter ⚠
p.Gly638Arg Single submitter ⚠
p.Gly642Ser Single submitter ⚠
p.Gly660Glu Single submitter ⚠
p.Gly683Glu Single submitter ⚠
p.Gly694Ala Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Gly76Asp Single submitter ⚠
p.Gly781Trp Single submitter ⚠
p.Gly93Ser Single submitter CDH15-related disorder ⚠
p.His335Arg Single submitter ⚠
p.His479Tyr Single submitter ⚠
p.His513Leu Single submitter ⚠
p.His513Tyr Single submitter ⚠
p.His548Gln Single submitter ⚠
p.His697Tyr Single submitter ⚠
p.Ile248Val Single submitter ⚠
p.Ile324Val Single submitter ⚠
p.Ile452Met Single submitter ⚠
p.Leu110Met Single submitter ⚠
p.Leu127Val Single submitter ⚠
p.Leu16Pro Single submitter ⚠
p.Leu228Gln Single submitter ⚠
p.Leu281Val Single submitter ⚠
p.Leu31Pro Single submitter ⚠
p.Leu380His Single submitter ⚠
p.Leu410= Single submitter
p.Leu422Pro Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Leu469Pro Single submitter ⚠
p.Leu502His Single submitter ⚠
p.Leu615Phe Single submitter ⚠
p.Leu680Gln Single submitter ⚠
p.Leu680Val Single submitter ⚠
p.Leu75Met Single submitter ⚠
p.Met1Lys Single submitter
p.Met235Val Single submitter ⚠
p.Phe157Leu Single submitter ⚠
p.Phe375Leu Single submitter ⚠
p.Phe5Cys Single submitter ⚠
p.Pro135His Single submitter CDH15-related disorder ⚠
p.Pro150Ser Single submitter ⚠
p.Pro28His Single submitter ⚠
p.Pro33Leu Single submitter ⚠
p.Pro389Ser Single submitter ⚠
p.Pro439Ala Single submitter ⚠
p.Pro439fs Single submitter
p.Pro439Leu Single submitter ⚠
p.Pro485Arg Single submitter ⚠
p.Pro487Arg Single submitter ⚠
p.Pro488Arg Single submitter ⚠
p.Pro51Leu Single submitter ⚠
p.Pro526Arg Single submitter ⚠
p.Pro551Arg Single submitter ⚠
p.Pro574= Single submitter
p.Pro681Leu Single submitter ⚠
p.Pro684Gln Single submitter ⚠
p.Pro692Leu Single submitter ⚠
p.Pro692Thr Single submitter ⚠
p.Pro701His Single submitter ⚠
p.Pro705Thr Single submitter ⚠
p.Pro708His Single submitter ⚠
p.Pro708Ser Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Pro726Arg Single submitter ⚠
p.Ser15Arg Single submitter ⚠
p.Ser203Cys Single submitter intellectual disability, autosomal dominant 3 ⚠
p.Ser291Phe Single submitter ⚠
p.Ser341Pro Single submitter ⚠
p.Ser535Arg Single submitter ⚠
p.Ser535Gly Single submitter ⚠
p.Ser707Arg Single submitter ⚠
p.Ser724Gly Single submitter ⚠
p.Ser744Trp Single submitter ⚠
p.Ser801Phe Single submitter ⚠
p.Thr131Ala Single submitter ⚠
p.Thr136Met Single submitter ⚠
p.Thr169Ser Single submitter ⚠
p.Thr184Arg Single submitter ⚠
p.Thr243Pro Single submitter ⚠
p.Thr261Asn Single submitter ⚠
p.Thr506Lys Single submitter ⚠
p.Thr506Met Single submitter ⚠
p.Thr600fs Single submitter CDH15-related disorder
p.Tyr170Phe Single submitter ⚠
p.Tyr412Cys Single submitter ⚠
p.Tyr416His Single submitter ⚠
p.Tyr737Cys Single submitter ⚠
p.Tyr763His Single submitter ⚠
p.Tyr765Ser Single submitter ⚠
p.Val142Ala Single submitter ⚠
p.Val161Leu Single submitter ⚠
p.Val214Gly Single submitter ⚠
p.Val223= Single submitter
p.Val321Gly Single submitter ⚠
p.Val340fs Single submitter
p.Val342Ala Single submitter ⚠
p.Val364Leu Single submitter ⚠
p.Val43Met Single submitter ⚠
p.Val482Leu Single submitter ⚠
p.Val539Ala Single submitter ⚠
p.Val54Leu Single submitter intellectual disability, autosomal dominant 1 ⚠
p.Val550Ala Single submitter ⚠
p.Val550Leu Single submitter ⚠
p.Val577Leu Single submitter ⚠
p.Val610Leu Single submitter ⚠
p.Val621Ile Single submitter ⚠
p.Val624Glu Single submitter ⚠
p.Val94Ala Single submitter ⚠
p.Val94Ile Single submitter ⚠
p.Asp185Glu No assertion criteria CDH15-related disorder ⚠