Sugi Variant

Sugi Variant/SOX2

SOX2 — 171 ClinVar variants

All ClinVar germline SOX2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 56 flagged for review →

46 Pathogenic · 3 Pathogenic/Likely pathogenic · 12 Likely pathogenic · 9 Conflicting · 12 Benign · 3 Benign/Likely benign · 23 Likely benign · 63 Uncertain significance

Full SOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 56

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.

Predicted LoF vs a conflicting call 1

ClinVar submitters conflict, and it's a predicted loss-of-function change in a gene where LoF causes disease — flagged for review, not resolved (verify NMD-escape for C-terminal truncations). Non-missense.

Predictors lean, ClinVar uncertain 39

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

Predictors split 12

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

All SOX2 variants

Pathogenic 46

  • p.Leu82fs Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr160Ter Multiple submitters SOX2-related disorder
  • p.Gly31fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ala281fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Arg113Trp Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Arg53fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gln155Ter Single submitter SOX2-related disorder
  • p.Gln177Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gln206_Tyr207insTer Single submitter
  • p.Glu104Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Glu8_Leu9insTer Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Glu86Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly130fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly135fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly185fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.His105fs Single submitter
  • p.Leu312fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Leu314fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Lys95Ter Single submitter
  • p.Phe48del Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro181fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro302fs Single submitter
  • p.Ser159_Tyr160insTer Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser18Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser257fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Trp166Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr110fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr110Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr180fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr2fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly20fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Arg56Gly No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Asn33fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gln182fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Glu6Ter No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Glu93Ter No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly20fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly21fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly280fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ile308fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Leu97Pro No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Met194_Gln195delinsIleTer No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Met1fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Met276fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro44Arg No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser315fs No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome

Pathogenic/Likely pathogenic 3

  • p.Asp123Gly Multiple submitters Developmental disorder
  • p.Glu8Ter Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr207Ter Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome

Likely pathogenic 12

  • p.Leu314fs Single submitter
  • p.Arg291Ter Single submitter
  • p.Arg96Pro Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gln195Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Glu285fs Single submitter
  • p.Gly31fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Phe48Val Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro253fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser259fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser300fs Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr200Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Val202fs Single submitter SOX2-related disorder

Conflicting classifications of pathogenicity 9

  • p.Ala191Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala287Pro Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Gln206Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Gly234Ser Single submitter Inborn genetic diseases ⚠
  • p.His297Arg Single submitter Inborn genetic diseases ⚠
  • p.Met217Ile Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Ser18= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Thr232Ala Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Thr85Met Single submitter Inborn genetic diseases ⚠

Benign 12

  • c.*469C>A Multiple submitters
  • c.*557G>A Multiple submitters
  • c.-31C>T Single submitter
  • c.*135dup Single submitter
  • c.*22G>A Single submitter
  • p.Ala151= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ala77= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Asn187Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Asp158Glu Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly219Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Thr116= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Thr126Met Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome

Benign/Likely benign 3

  • p.Ala287= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Leu278= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Val303= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome

Likely benign 23

  • p.Ala281= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Asn164= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Asn187= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly280= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Leu81= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro11= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser290Thr Multiple submitters Inborn genetic diseases
  • p.Thr311= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Val50= Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • c.*337A>G Single submitter
  • p.Ala147= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ala191= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ala267Thr Single submitter
  • p.Gly13= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly185= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.His297Asp Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Leu312= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Met194Leu Single submitter
  • p.Met240Val Single submitter
  • p.Met276Ile Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Pro279= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro284= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro304= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome

Uncertain significance 63

  • p.Ala267Val Multiple submitters Inborn genetic diseases ⚠
  • p.Gly142Arg Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Leu81Phe Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Pro264Thr Multiple submitters Inborn genetic diseases ⚠
  • p.Ser37Ile Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Thr26Ala Multiple submitters anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Val202Met Multiple submitters Inborn genetic diseases ⚠
  • c.*5C>G Single submitter
  • c.*6G>C Single submitter
  • p.Ala192Gly Single submitter ⚠
  • p.Ala248Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Ala281Gly Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Ala287Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala29Thr Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Ala30_Gly31insAla Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Arg56Pro Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Arg56Trp Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Asn154Lys Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Asn309Tyr Single submitter ⚠
  • p.Asn46Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Asn68Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Asp107_Pro112delinsValPheIleIle Single submitter
  • p.Asp272Asn Single submitter ⚠
  • p.Gln229His Single submitter ⚠
  • p.Gln230Leu Single submitter ⚠
  • p.Gln299His Single submitter Inborn genetic diseases ⚠
  • p.Gln34Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly169Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Gly190Ser Single submitter Inborn genetic diseases ⚠
  • p.Gly19Arg Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Gly23= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly231Val Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Gly241Ser Single submitter Inborn genetic diseases ⚠
  • p.Gly54Trp Single submitter ⚠
  • p.His293Asn Single submitter ⚠
  • p.His293Tyr Single submitter ⚠
  • p.Leu186Phe Single submitter Inborn genetic diseases ⚠
  • p.Leu314= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Leu314Val Single submitter Inborn genetic diseases ⚠
  • p.Met197Ile Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Met240Arg Single submitter Inborn genetic diseases ⚠
  • p.Met273Ile Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Met294Leu Single submitter ⚠
  • p.Met45Leu Single submitter ⚠
  • p.Pro12= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro221Arg Single submitter Inborn genetic diseases ⚠
  • p.Pro221Ser Single submitter Inborn genetic diseases ⚠
  • p.Pro252= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Pro253Ala Single submitter ⚠
  • p.Pro264Ser Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome ⚠
  • p.Ser220Ter Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser246= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Ser250Cys Single submitter ⚠
  • p.Thr215Ser Single submitter Inborn genetic diseases ⚠
  • p.Thr256Ile Single submitter Inborn genetic diseases ⚠
  • p.Thr7= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Thr85= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr200= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Tyr200Cys Single submitter ⚠
  • p.Val255Ala Single submitter Inborn genetic diseases ⚠
  • p.Val283= Single submitter anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Gly23dup No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome
  • p.Met197Val No assertion criteria anophthalmia/microphthalmia-esophageal atresia syndrome ⚠