Sugi Variant

Sugi Variant/HECW2

HECW2 — 648 ClinVar variants

All ClinVar germline HECW2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 344 flagged for review →

8 Pathogenic · 3 Pathogenic/Likely pathogenic · 30 Likely pathogenic · 25 Conflicting · 24 Benign · 20 Benign/Likely benign · 181 Likely benign · 357 Uncertain significance

Full HECW2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 344

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 4

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

Predictors agree, ClinVar conflicts 20

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

Predictors lean, ClinVar uncertain 231

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 231

Predictors split 89

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

All HECW2 variants

Pathogenic 8

  • p.Arg1191Gln Multiple submitters Inborn genetic diseases
  • p.Arg1330Trp Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Arg1444Thr Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Glu1445Gln Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Lys1196Arg Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Tyr1201fs Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Arg246Ter No assertion criteria neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Phe1193Val No assertion criteria neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠

Pathogenic/Likely pathogenic 3

  • p.Arg1495Ser Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Asn1199Lys Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ser1505Thr Multiple submitters Inborn genetic diseases ⚠

Likely pathogenic 30

  • p.Arg1191Trp Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Asn1199Ser Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Leu1448Ser Multiple submitters HECW2-related disorders
  • p.Ser1504Tyr Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Tyr863His Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Ala1181Gly Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Ala1195Pro Single submitter Inborn genetic diseases
  • p.Arg1515Ter Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Arg271Cys Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Arg291Ter Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Arg861Trp Single submitter
  • p.Arg899Ter Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Asp1350Tyr Single submitter Neurodevelopmental disorder with hypotonia
  • p.Asp806Asn Single submitter HECW2-related disorders ⚠
  • p.Gln1498Glu Single submitter HECW2-related disorders
  • p.Glu1491Gln Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Glu1564Lys Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Glu1572Lys Single submitter Inborn genetic diseases
  • p.Gly1452Ala Single submitter
  • p.Gly1452Val Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Gly1502Ala Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ile138Val Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Leu1314His Single submitter
  • p.Leu1448Trp Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Phe1327Ser Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Phe1328Leu Single submitter HECW2-related disorders
  • p.Phe1441Leu Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ser1504Ala Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language ⚠
  • p.Thr1503Ala Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Tyr1277His Single submitter neurodevelopmental disorder with hypotonia, seizures, and absent language

Conflicting classifications of pathogenicity 25

Benign 24

  • c.2435-7C>T Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • c.2814+29G>A Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • c.2814+37G>A Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • c.400+15G>A Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • c.*37G>T Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ala749= Multiple submitters
  • p.Arg900= Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Asn178Ser Multiple submitters intellectual disability
  • p.Asn238= Multiple submitters
  • p.Glu56= Multiple submitters
  • p.His311= Multiple submitters
  • p.Leu1340= Multiple submitters
  • p.Pro134Ser Multiple submitters
  • p.Pro431= Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ser1148= Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Thr116Ile Multiple submitters ⚠
  • c.2338+8A>G Single submitter
  • p.Ala63= Single submitter
  • p.Asn426Ser Single submitter
  • p.Gln72= Single submitter
  • p.Ile338Leu Single submitter
  • p.Ile489Leu Single submitter
  • p.Val1057Ile Single submitter
  • p.Gly128= No assertion criteria HECW2-related disorder

Benign/Likely benign 20

  • c.3000+7C>T Multiple submitters
  • c.3238+9T>C Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • c.3650+9_3650+10del Multiple submitters
  • p.Ala747Pro Multiple submitters Inborn genetic diseases
  • p.Ala747Val Multiple submitters Inborn genetic diseases
  • p.Arg448del Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Arg659Gln Multiple submitters
  • p.Arg740Ser Multiple submitters Inborn genetic diseases
  • p.Asn1394Ser Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Asn1518= Multiple submitters
  • p.Asn417Ser Multiple submitters Inborn genetic diseases
  • p.Asp354= Multiple submitters Inborn genetic diseases
  • p.Gln1420= Multiple submitters
  • p.Gly761Glu Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Ile1414= Multiple submitters
  • p.Leu743= Multiple submitters
  • p.Pro332= Multiple submitters neurodevelopmental disorder with hypotonia, seizures, and absent language
  • p.Thr1539= Multiple submitters
  • p.Thr406Ile Multiple submitters
  • p.Thr69= Multiple submitters

Likely benign 181

Uncertain significance 357

Showing the top 300 by review status; the full set is in the sitemap.