ESAM — 78 ClinVar variants

All ClinVar germline ESAM variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 59 flagged for review →

1 Pathogenic · 7 Likely pathogenic · 1 Benign · 11 Likely benign · 58 Uncertain significance

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

⚑ Evidence disagreements 59

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 lean, ClinVar uncertain 30

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

Predictors split 29

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

All ESAM variants

Pathogenic 1

c.70+1G>T Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity

Likely pathogenic 7

c.451+1G>A Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
c.608-1G>A Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
p.Arg317Ter Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
p.Arg39fs Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
p.Cys158Ter Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
p.Leu12Ter Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
p.Pro96fs Single submitter neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity

Benign 1

c.731-9C>A Multiple submitters

Likely benign 11

p.Arg107Trp Single submitter ⚠
p.Arg159His Single submitter
p.Gly6Arg Single submitter
p.His272Gln Single submitter
p.Ile290Val Single submitter
p.Leu13= Single submitter
p.Leu150= Single submitter
p.Leu31= Single submitter
p.Leu8Pro Single submitter
p.Pro181= Single submitter
p.Pro26= Single submitter

Uncertain significance 58

p.Ala182Thr Single submitter ⚠
p.Ala22Val Single submitter ⚠
p.Ala24Glu Single submitter ⚠
p.Ala251Val Single submitter ⚠
p.Ala318Thr Single submitter ⚠
p.Arg159Cys Single submitter ⚠
p.Arg273His Single submitter ⚠
p.Arg274Gln Single submitter ⚠
p.Arg274Gly Single submitter ⚠
p.Arg274Trp Single submitter ⚠
p.Arg372His Single submitter ⚠
p.Asn283Ser Single submitter ⚠
p.Asn38Asp Single submitter ⚠
p.Asp284Tyr Single submitter ⚠
p.Gln383Arg Single submitter ⚠
p.Gln41Glu Single submitter ⚠
p.Glu229Asp Single submitter ⚠
p.Gly115Val Single submitter ⚠
p.Gly139Asp Single submitter ⚠
p.Gly207Glu Single submitter ⚠
p.Gly324Val Single submitter ⚠
p.Gly329Arg Single submitter ⚠
p.Gly329Asp Single submitter ⚠
p.Gly352Val Single submitter ⚠
p.Gly46Arg Single submitter ⚠
p.Gly58Arg Single submitter ⚠
p.His323Tyr Single submitter ⚠
p.Ile205Val Single submitter ⚠
p.Leu116Pro Single submitter ⚠
p.Leu172Pro Single submitter ⚠
p.Lys143Glu Single submitter ⚠
p.Lys80Arg Single submitter ⚠
p.Met104Thr Single submitter ⚠
p.Pro177Ser Single submitter ⚠
p.Pro245Ser Single submitter ⚠
p.Pro25His Single submitter ⚠
p.Pro25Leu Single submitter ⚠
p.Pro296Thr Single submitter ⚠
p.Pro345Ser Single submitter ⚠
p.Pro5Leu Single submitter ⚠
p.Pro69Ser Single submitter ⚠
p.Pro96Leu Single submitter ⚠
p.Ser103Phe Single submitter ⚠
p.Ser127Phe Single submitter ⚠
p.Ser141Gly Single submitter ⚠
p.Ser215Leu Single submitter ⚠
p.Ser21Arg Single submitter ⚠
p.Ser27Leu Single submitter ⚠
p.Ser61Phe Single submitter ⚠
p.Thr10Ile Single submitter ⚠
p.Thr232Ala Single submitter ⚠
p.Thr238Ala Single submitter ⚠
p.Thr257Ala Single submitter ⚠
p.Thr349Met Single submitter ⚠
p.Thr93Ala Single submitter ⚠
p.Val130Met Single submitter ⚠
p.Val149Ala Single submitter ⚠
p.Val380Met Single submitter ⚠