Sugi Variant

Sugi Variant/PAK1

PAK1 — 161 ClinVar variants

All ClinVar germline PAK1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 81 flagged for review →

2 Pathogenic · 2 Pathogenic/Likely pathogenic · 20 Likely pathogenic · 2 Conflicting · 6 Benign · 23 Likely benign · 106 Uncertain significance

Full PAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 81

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 1

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

Predictors agree, ClinVar conflicts 2

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

Predictors lean, ClinVar uncertain 60

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

Predictors split 18

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

All PAK1 variants

Pathogenic 2

  • p.Pro121Leu Multiple submitters PAK1-related disorder
  • p.Tyr131Asn Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay

Pathogenic/Likely pathogenic 2

  • p.Ile476Thr Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Pro121Ser Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay

Likely pathogenic 20

  • p.Leu470Arg Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Met143Thr Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Glu372Ala Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Ile312Phe Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Leu465Phe Single submitter PAK1-related disorder
  • p.Leu470Gln Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Lys70fs Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Met143Lys Single submitter
  • p.Met143Val Single submitter
  • p.Ser110Thr Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Ser133Pro Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Tyr131Cys Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Tyr142His Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Tyr429Cys Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Tyr474His Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Val284Met Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Arg105Cys No assertion criteria intellectual developmental disorder with macrocephaly, seizures, and speech delay ⚠
  • p.Arg371Cys No assertion criteria intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Ile476Val No assertion criteria intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Thr84Arg No assertion criteria intellectual developmental disorder with macrocephaly, seizures, and speech delay

Conflicting classifications of pathogenicity 2

  • p.Arg421Trp Single submitter Inborn genetic diseases ⚠
  • p.Val127Met Single submitter intellectual developmental disorder with macrocephaly, seizures, and speech delay ⚠

Benign 6

  • c.1116+8C>G Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • c.999-12G>A Multiple submitters intellectual developmental disorder with macrocephaly, seizures, and speech delay
  • p.Lys119= Multiple submitters
  • p.Asp183_Ala184insAsp Single submitter
  • p.Ser115= Single submitter
  • p.Thr97= No assertion criteria PAK1-related disorder

Likely benign 23

Uncertain significance 106