EPB41L1 — 222 ClinVar variants

All ClinVar germline EPB41L1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 113 flagged for review →

1 Likely pathogenic · 9 Conflicting · 13 Benign · 9 Benign/Likely benign · 65 Likely benign · 125 Uncertain significance

Full EPB41L1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 113

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 1

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

EPB41L1 p.Arg638Cys Likely pathogenic Single submitter
Abnormal brain morphology

Predictors agree, ClinVar conflicts 6

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

EPB41L1 p.Ala554Asp Conflicting Single submitter
intellectual disability, autosomal dominant 11
EPB41L1 p.Arg465Gln Conflicting Single submitter
EPB41L1 p.Asp451Ala Conflicting Single submitter
EPB41L1 p.Asp644Asn Conflicting Single submitter
EPB41L1 p.Asp660His Conflicting Single submitter
EPB41L1 p.Thr591Met Conflicting Single submitter

Predictors lean, ClinVar uncertain 92

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

Predictors split 14

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

All EPB41L1 variants

Likely pathogenic 1

p.Arg638Cys Single submitter Abnormal brain morphology ⚠

Conflicting classifications of pathogenicity 9

p.Ala554Asp Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Arg429His Single submitter
p.Arg465Gln Single submitter ⚠
p.Arg536Cys Single submitter
p.Asp451Ala Single submitter ⚠
p.Asp644Asn Single submitter ⚠
p.Asp660His Single submitter ⚠
p.Ser631= Single submitter
p.Thr591Met Single submitter ⚠

Benign 13

p.Glu185= Multiple submitters
p.Glu256= Multiple submitters
p.Leu194= Multiple submitters
p.Pro547Arg Multiple submitters
p.Ser441= Multiple submitters
p.Thr623= Multiple submitters
c.1026+10C>T Single submitter
c.1669-1775C>A Single submitter
c.1669-3105C>T Single submitter
c.1669-3415A>C Single submitter
c.873+7C>G Single submitter
p.Arg572Cys Single submitter
p.His446= Single submitter

Benign/Likely benign 9

p.Arg394= Multiple submitters
p.Arg645Gln Multiple submitters
p.Glu513= Multiple submitters
p.His37= Multiple submitters
p.Lys548Arg Multiple submitters
p.Phe242= Multiple submitters
p.Pro177= Multiple submitters
p.Pro415= Multiple submitters
p.Thr399= Multiple submitters

Likely benign 65

p.Asn555Ser Multiple submitters
p.Glu467= Multiple submitters
p.Gly301= Multiple submitters
p.Pro484Leu Multiple submitters
p.Pro542= Multiple submitters
p.Ser107Ala Multiple submitters
p.Ser564= Multiple submitters
c.1300+22_1300+26del Single submitter
c.1485+18T>A Single submitter
c.1668+10G>A Single submitter
c.1668+9C>T Single submitter
c.1669-2909C>T Single submitter
c.1669-2946C>T Single submitter
c.177+11G>A Single submitter
c.2079+13T>C Single submitter
c.2269-12T>C Single submitter
c.2269-15C>T Single submitter
c.2440-9C>G Single submitter
c.2521-12C>T Single submitter
c.2638-4C>T Single submitter
c.343-6C>T Single submitter
c.566+7G>A Single submitter
c.566+8C>T Single submitter
c.567-14T>C Single submitter
c.786-10T>C Single submitter
c.-10+12972C>T Single submitter
p.Ala543Pro Single submitter
p.Ala71= Single submitter
p.Arg394Trp Single submitter
p.Arg474Gly Single submitter
p.Asn597= Single submitter
p.Asp124= Single submitter
p.Asp582Asn Single submitter
p.Cys127= Single submitter
p.Glu134= Single submitter
p.Glu750= Single submitter
p.His492= Single submitter
p.Ile824= Single submitter
p.Leu314= Single submitter
p.Leu482= Single submitter
p.Leu538= Single submitter
p.Leu594Pro Single submitter
p.Leu643= Single submitter
p.Leu760= Single submitter
p.Lys330= Single submitter
p.Phe138= Single submitter
p.Pro545= Single submitter
p.Pro687Leu Single submitter
p.Pro80= Single submitter
p.Ser544Thr Single submitter
p.Ser650= Single submitter
p.Ser75Leu Single submitter ⚠
p.Ser86= Single submitter
p.Ser870= Single submitter
p.Thr778Ala Single submitter
p.Tyr261= Single submitter
p.Tyr283= Single submitter
c.2079+5A>G No assertion criteria EPB41L1-related disorder
c.2269_2271del No assertion criteria intellectual disability
p.Ala414= No assertion criteria EPB41L1-related disorder
p.Arg534Trp No assertion criteria intellectual disability
p.Ile787= No assertion criteria EPB41L1-related disorder
p.Pro679= No assertion criteria EPB41L1-related disorder
p.Ser650Leu No assertion criteria EPB41L1-related disorder
p.Val442Asp No assertion criteria intellectual disability

Uncertain significance 125

p.Ala440Pro Multiple submitters
p.Ser44Pro Multiple submitters intellectual disability, autosomal dominant 11 ⚠
p.Thr247Ser Multiple submitters ⚠
p.Val736Ala Multiple submitters intellectual disability, autosomal dominant 11 ⚠
c.1026+4A>G Single submitter intellectual disability, autosomal dominant 11
c.1300+4T>G Single submitter
c.2079+4C>T Single submitter
c.2268+4A>G Single submitter
c.2356-2A>G Single submitter intellectual disability, autosomal dominant 11
c.-15+11729G>A Single submitter intellectual disability, autosomal dominant 11
p.Ala18Thr Single submitter ⚠
p.Ala198Thr Single submitter ⚠
p.Ala222Val Single submitter ⚠
p.Ala269Gly Single submitter ⚠
p.Ala27Thr Single submitter ⚠
p.Ala401Thr Single submitter ⚠
p.Ala440Gly Single submitter ⚠
p.Ala543Thr Single submitter ⚠
p.Ala57Val Single submitter ⚠
p.Ala632Thr Single submitter ⚠
p.Ala849Asp Single submitter complex neurodevelopmental disorder ⚠
p.Ala91Ser Single submitter ⚠
p.Ala97Val Single submitter ⚠
p.Arg118Gln Single submitter ⚠
p.Arg311Gln Single submitter ⚠
p.Arg318His Single submitter ⚠
p.Arg429Cys Single submitter ⚠
p.Arg438His Single submitter ⚠
p.Arg455Gln Single submitter ⚠
p.Arg530Gln Single submitter ⚠
p.Arg534Gln Single submitter ⚠
p.Arg55Trp Single submitter ⚠
p.Arg574Trp Single submitter ⚠
p.Arg603Cys Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Arg659Gln Single submitter ⚠
p.Arg659Trp Single submitter ⚠
p.Arg6Lys Single submitter intellectual disability, autosomal dominant 11
p.Asn245Lys Single submitter ⚠
p.Asn43Lys Single submitter ⚠
p.Asn45Asp Single submitter ⚠
p.Asn512Ser Single submitter
p.Asn555Asp Single submitter ⚠
p.Asp286Glu Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Asp582Tyr Single submitter ⚠
p.Asp837Gly Single submitter ⚠
p.Asp875Glu Single submitter ⚠
p.Asp875Tyr Single submitter ⚠
p.Asp8Asn Single submitter ⚠
p.Cys143Tyr Single submitter ⚠
p.Cys684Arg Single submitter ⚠
p.Gln774Glu Single submitter ⚠
p.Glu128Lys Single submitter intellectual disability, autosomal dominant 11
p.Glu223Gln Single submitter ⚠
p.Glu23Lys Single submitter ⚠
p.Glu41Asp Single submitter ⚠
p.Glu444Lys Single submitter ⚠
p.Glu469Lys Single submitter ⚠
p.Glu535Gln Single submitter ⚠
p.Glu562Lys Single submitter ⚠
p.Glu577_Ser578insTer Single submitter
p.Glu588Val Single submitter
p.Glu617Asp Single submitter ⚠
p.Glu634Lys Single submitter
p.Glu653Ala Single submitter ⚠
p.Glu653Lys Single submitter ⚠
p.Glu834Lys Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Gly225Asp Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Gly38Ser Single submitter ⚠
p.Gly452Ser Single submitter ⚠
p.Gly626Asp Single submitter
p.Gly673Arg Single submitter ⚠
p.Gly674Asp Single submitter ⚠
p.His129Tyr Single submitter ⚠
p.His272Arg Single submitter ⚠
p.His288Tyr Single submitter intellectual disability, autosomal dominant 11 ⚠
p.His370Arg Single submitter ⚠
p.His810Leu Single submitter ⚠
p.Ile271Val Single submitter ⚠
p.Ile675Thr Single submitter ⚠
p.Ile747Thr Single submitter ⚠
p.Ile752Thr Single submitter ⚠
p.Ile786Met Single submitter ⚠
p.Ile90Val Single submitter ⚠
p.Leu655= Single submitter
p.Leu655Pro Single submitter ⚠
p.Leu661Pro Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Lys160Arg Single submitter ⚠
p.Lys66Arg Single submitter ⚠
p.Lys876Arg Single submitter ⚠
p.Met255Val Single submitter ⚠
p.Met264Leu Single submitter ⚠
p.Met63Thr Single submitter ⚠
p.Phe138Leu Single submitter ⚠
p.Phe740Ile Single submitter ⚠
p.Pro19= Single submitter
p.Pro379Leu Single submitter ⚠
p.Pro382Arg Single submitter ⚠
p.Pro40Gln Single submitter ⚠
p.Pro713Leu Single submitter ⚠
p.Pro713Ser Single submitter ⚠
p.Pro785Leu Single submitter
p.Pro87Ser Single submitter ⚠
p.Ser396Gly Single submitter ⚠
p.Ser437Phe Single submitter ⚠
p.Ser443Asn Single submitter ⚠
p.Ser466Thr Single submitter ⚠
p.Ser615Thr Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Ser631Ile Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Ser648Asn Single submitter ⚠
p.Ser650Thr Single submitter ⚠
p.Ser784Cys Single submitter ⚠
p.Thr426Pro Single submitter
p.Thr488Ala Single submitter ⚠
p.Thr54Met Single submitter ⚠
p.Thr623Ala Single submitter ⚠
p.Thr652Ser Single submitter ⚠
p.Thr749Met Single submitter ⚠
p.Trp532Gly Single submitter ⚠
p.Tyr864Cys Single submitter
p.Val113Met Single submitter
p.Val126Ala Single submitter intellectual disability, autosomal dominant 11 ⚠
p.Val285Leu Single submitter ⚠
p.Val721Phe Single submitter ⚠
p.Ala665Val No assertion criteria EPB41L1-related disorder ⚠
p.His853Tyr No assertion criteria intellectual disability, autosomal dominant 11 ⚠