SOX3 — 113 ClinVar variants

All ClinVar germline SOX3 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 56 flagged for review →

2 Pathogenic · 1 Likely pathogenic · 5 Conflicting · 3 Benign · 5 Benign/Likely benign · 30 Likely benign · 67 Uncertain significance

Full SOX3 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 3

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

SOX3 p.Arg5Pro Conflicting Single submitter
intellectual disability, X-linked, with panhypopituitarism
SOX3 p.Gly316Ser Conflicting Single submitter
panhypopituitarism, X-linked
SOX3 p.Met365Leu Conflicting Single submitter

Predictors lean, ClinVar uncertain 44

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

Predictors split 9

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

All SOX3 variants

Pathogenic 2

p.Ala248_Ser249insAlaAlaAlaAlaAlaAlaAla No assertion criteria panhypopituitarism, X-linked
p.Ala248_Ser249insAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAla No assertion criteria X-linked intellectual disability with isolated growth hormone deficiency

Likely pathogenic 1

p.Ser150Tyr No assertion criteria intellectual disability, X-linked, with panhypopituitarism

Conflicting classifications of pathogenicity 5

p.Ala240_Ala248del Single submitter intellectual disability
p.Arg5Pro Single submitter intellectual disability, X-linked, with panhypopituitarism ⚠
p.Gly104Arg Single submitter
p.Gly316Ser Single submitter panhypopituitarism, X-linked ⚠
p.Met365Leu Single submitter ⚠

Benign 3

p.Ala244= Multiple submitters
p.Tyr203= Multiple submitters
p.Asp190= Single submitter

Benign/Likely benign 5

p.Ala412= Multiple submitters
p.Ala415Thr Multiple submitters
p.Lys201= Multiple submitters
p.Pro103Thr Multiple submitters
p.Pro251= Multiple submitters panhypopituitarism, X-linked

Likely benign 30

p.Ala240= Multiple submitters
p.Ala247_Ala248del Multiple submitters
p.Gly334= Multiple submitters
p.Ser224= Multiple submitters
p.Ala111= Single submitter
p.Ala117= Single submitter
p.Ala242_Ala248del Single submitter
p.Ala244_Ala248del Single submitter
p.Ala305= Single submitter
p.Ala326= Single submitter
p.Ala329= Single submitter
p.Ala343= Single submitter
p.Ala356= Single submitter
p.Ala361_Ala364del Single submitter
p.Arg196= Single submitter
p.Asp182= Single submitter
p.Glu191= Single submitter
p.Leu218= Single submitter
p.Met336Leu Single submitter
p.Pro298Gln Single submitter
p.Pro315= Single submitter
p.Ser227Gly Single submitter
p.Tyr281= Single submitter
p.Tyr309= Single submitter
p.Val323Ala Single submitter
c.*5C>T No assertion criteria SOX3-related disorder
p.Ala241_Ala248del No assertion criteria SOX3-related disorder
p.Ala358= No assertion criteria SOX3-related disorder
p.Asp396= No assertion criteria SOX3-related disorder
p.Pro294del No assertion criteria SOX3-related disorder

Uncertain significance 67

p.Ala113Thr Multiple submitters intellectual disability, X-linked, with panhypopituitarism ⚠
p.Ala248dup Multiple submitters intellectual disability, X-linked, with panhypopituitarism
p.Asn322Lys Multiple submitters ⚠
p.Asn7Ser Multiple submitters intellectual disability, X-linked, with panhypopituitarism ⚠
p.Gln283Pro Multiple submitters ⚠
p.Gly133Val Multiple submitters ⚠
p.Leu229Phe Multiple submitters ⚠
p.Met336Ile Multiple submitters ⚠
p.Ser319Asn Multiple submitters ⚠
p.Ala102Val Single submitter ⚠
p.Ala111Thr Single submitter intellectual disability, X-linked, with panhypopituitarism ⚠
p.Ala243_Ala248del Single submitter
p.Ala246_Ala248del Single submitter
p.Ala248del Single submitter
p.Ala359Val Single submitter ⚠
p.Ala362Thr Single submitter ⚠
p.Ala411Val Single submitter ⚠
p.Ala414Thr Single submitter ⚠
p.Ala433Ser Single submitter premature menopause ⚠
p.Arg422His Single submitter intellectual disability, X-linked, with panhypopituitarism ⚠
p.Asn161Lys Single submitter ⚠
p.Asp205Asn Single submitter ⚠
p.Asp396Asn Single submitter ⚠
p.Gly104Ala Single submitter ⚠
p.Gly107Ala Single submitter ⚠
p.Gly107Asp Single submitter
p.Gly125Asp Single submitter ⚠
p.Gly129Ala Single submitter ⚠
p.Gly266Asp Single submitter ⚠
p.Gly266Ser Single submitter ⚠
p.Gly335Val Single submitter ⚠
p.Gly89Arg Single submitter ⚠
p.Gly96Asp Single submitter ⚠
p.Gly98Ser Single submitter ⚠
p.His300Tyr Single submitter ⚠
p.His388= Single submitter
p.Ile446Met Single submitter panhypopituitarism, X-linked
p.Lys140Arg Single submitter ⚠
p.Met200Leu Single submitter ⚠
p.Met287Ile Single submitter ⚠
p.Met299Leu Single submitter ⚠
p.Met312Val Single submitter ⚠
p.Met370Thr Single submitter ⚠
p.Pro103Leu Single submitter ⚠
p.Pro142Ser Single submitter ⚠
p.Pro284His Single submitter ⚠
p.Pro284Ser Single submitter ⚠
p.Pro285Ala Single submitter ⚠
p.Pro285Gln Single submitter ⚠
p.Pro293Leu Single submitter ⚠
p.Pro294_Ala295insPro Single submitter
p.Pro297= Single submitter
p.Pro314Arg Single submitter ⚠
p.Pro352= Single submitter
p.Pro419Leu Single submitter ⚠
p.Ser110Gly Single submitter ⚠
p.Ser250Cys Single submitter ⚠
p.Ser286Gly Single submitter ⚠
p.Ser286Thr Single submitter ⚠
p.Ser288Gly Single submitter ⚠
p.Thr354_Ala359del Single submitter
p.Thr354Pro Single submitter ⚠
p.Val198Leu Single submitter
p.Val252Met Single submitter ⚠
p.Val264Gly Single submitter intellectual disability, X-linked, with panhypopituitarism
p.Val323Asp Single submitter ⚠
p.Ala248_Ser249insAlaAla No assertion criteria SOX3-related disorder