GDNF — 125 ClinVar variants

All ClinVar germline GDNF variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 28 flagged for review →

4 Conflicting · 26 Benign · 3 Benign/Likely benign · 20 Likely benign · 72 Uncertain significance

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

⚑ Evidence disagreements 28

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 2

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

GDNF p.Ala98Ser Conflicting Single submitter
Hirschsprung disease, susceptibility to, 3
GDNF p.Arg104Gly Conflicting Single submitter

Predictors lean, ClinVar uncertain 21

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

Predictors split 5

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

GDNF p.Arg93Trp Benign/Likely benign Multiple submitters
Hirschsprung disease, susceptibility to, 3
GDNF p.Pro21Ser Uncertain significance Multiple submitters
Hirschsprung disease, susceptibility to, 3
GDNF p.Asp63Tyr Uncertain significance Single submitter
GDNF p.His15Pro Uncertain significance Single submitter
GDNF p.Ile211Met Uncertain significance Single submitter
Hirschsprung disease, susceptibility to, 3

All GDNF variants

Conflicting classifications of pathogenicity 4

c.*5G>A Single submitter Hirschsprung disease, susceptibility to, 3
p.Ala46= Single submitter
p.Ala98Ser Single submitter Hirschsprung disease, susceptibility to, 3 ⚠
p.Arg104Gly Single submitter ⚠

Benign 26

c.152-73C>T Multiple submitters
c.-51A>G Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*1264C>T Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*1605T>C Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*1651A>G Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*2162G>T Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*2204G>T Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*363A>T Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*529G>A Multiple submitters Hirschsprung disease, susceptibility to, 3
p.Arg180= Multiple submitters Hirschsprung disease, susceptibility to, 3
c.152-251G>A Single submitter
c.152-318G>A Single submitter
c.*1004T>C Single submitter Hirschsprung disease, susceptibility to, 3
c.*1141C>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1199A>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*131GGA[10] Single submitter
c.*131GGA[12] Single submitter
c.*131GGA[9] Single submitter
c.*1389A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*1541T>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1785G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1898C>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2643C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*2713G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2883G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*450C>T Single submitter Hirschsprung disease, susceptibility to, 3

Benign/Likely benign 3

p.Arg143= Multiple submitters Hirschsprung disease, susceptibility to, 3
p.Arg93Trp Multiple submitters Hirschsprung disease, susceptibility to, 3 ⚠
p.Asp150Asn Multiple submitters Hirschsprung disease, susceptibility to, 3

Likely benign 20

c.*93A>T Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*988A>G Multiple submitters Hirschsprung disease, susceptibility to, 3
p.Arg74= Multiple submitters Hirschsprung disease, susceptibility to, 3
p.Cys149= Multiple submitters Hirschsprung disease, susceptibility to, 3
c.151+9C>T Single submitter
c.*1276A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*1375T>C Single submitter Hirschsprung disease, susceptibility to, 3
c.*1406G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1592G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1693G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1782G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2014G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2150T>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*2440G>A Single submitter Hirschsprung disease, susceptibility to, 3
p.Asn115= Single submitter
p.Ile123Val Single submitter
p.Lys26= Single submitter
p.Thr155Met Single submitter
c.-26-10G>T No assertion criteria GDNF-related disorder
p.Phe61= No assertion criteria GDNF-related disorder

Uncertain significance 72

c.*2213G>A Multiple submitters Hirschsprung disease, susceptibility to, 3
c.*2828T>A Multiple submitters Hirschsprung disease, susceptibility to, 3
p.Arg116Gln Multiple submitters Hirschsprung disease, susceptibility to, 3 ⚠
p.Pro21Ser Multiple submitters Hirschsprung disease, susceptibility to, 3 ⚠
c.151+9C>G Single submitter Hirschsprung disease, susceptibility to, 3
c.-132G>C Single submitter Hirschsprung disease, susceptibility to, 3
c.-26-811G>T Single submitter Hirschsprung disease
c.-26G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.-34G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.-42G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*116G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1244A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*1246C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*128_*133del Single submitter
c.*131G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1331G>C Single submitter Hirschsprung disease, susceptibility to, 3
c.*1360A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*1433A>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1534G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1540A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*1587G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1612C>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1627C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1657C>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1699G>C Single submitter Hirschsprung disease, susceptibility to, 3
c.*1713C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*1788G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*1927C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*2059C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*2119C>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*2265T>C Single submitter Hirschsprung disease, susceptibility to, 3
c.*2267G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2318G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*235G>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*2446G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2556T>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*2646C>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*2651C>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*2829_*2830del Single submitter
c.*346C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*532A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*617A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*717T>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*795C>T Single submitter Hirschsprung disease, susceptibility to, 3
c.*807G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*907G>A Single submitter Hirschsprung disease, susceptibility to, 3
c.*912A>G Single submitter Hirschsprung disease, susceptibility to, 3
c.*958A>C Single submitter Hirschsprung disease, susceptibility to, 3
p.Ala122Ser Single submitter ⚠
p.Ala33Ser Single submitter ⚠
p.Arg168Lys Single submitter ⚠
p.Arg41Ser Single submitter ⚠
p.Arg91Gln Single submitter Hirschsprung disease, susceptibility to, 3 ⚠
p.Asn52Lys Single submitter ⚠
p.Asp62Asn Single submitter ⚠
p.Asp63Tyr Single submitter ⚠
p.Glu153Lys Single submitter ⚠
p.Gly107Arg Single submitter ⚠
p.Gly175Ala Single submitter ⚠
p.Gly25Ser Single submitter ⚠
p.Gly39Arg Single submitter ⚠
p.His15Pro Single submitter ⚠
p.Ile211Met Single submitter Hirschsprung disease, susceptibility to, 3 ⚠
p.Leu130Phe Single submitter Hirschsprung disease, susceptibility to, 3 ⚠
p.Leu38Pro Single submitter ⚠
p.Lys73Glu Single submitter ⚠
p.Phe190Cys Single submitter ⚠
p.Phe45Leu Single submitter ⚠
p.Thr154Lys Single submitter ⚠
p.Tyr57His Single submitter ⚠
p.Val170Met Single submitter GDNF-related disorder ⚠
p.Gly209_Cys210del No assertion criteria Hirschsprung disease, susceptibility to, 1