Sugi Variant

Sugi Variant/CNOT3

CNOT3 — 428 ClinVar variants

All ClinVar germline CNOT3 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 198 flagged for review →

40 Pathogenic · 3 Pathogenic/Likely pathogenic · 26 Likely pathogenic · 18 Conflicting · 24 Benign · 12 Benign/Likely benign · 97 Likely benign · 208 Uncertain significance

Full CNOT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 198

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 12

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

Predictors lean, ClinVar uncertain 106

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

Predictors split 79

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

All CNOT3 variants

Pathogenic 40

  • p.Arg697Ter Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Asn276fs Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Tyr648fs Multiple submitters
  • p.Val660fs Multiple submitters
  • c.1406+1G>A Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • c.1705+2T>G Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • c.1706-2A>G Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • c.387+1G>A Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • c.388-1G>C Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ala345fs Single submitter Inborn genetic diseases
  • p.Ala376fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Arg57Trp Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Asp630_Ser631insTer Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gln24Ter Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gln256Ter Single submitter
  • p.Gln8Ter Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Glu26fs Single submitter Inborn genetic diseases
  • p.Glu632fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gly397Ter Single submitter Inborn genetic diseases
  • p.Gly481fs Single submitter Inborn genetic diseases
  • p.Gly493fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Leu196fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Lys31Ter Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Lys682fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Met189fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Pro390fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Pro458fs Single submitter
  • p.Pro537fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser310fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser411fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser415fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser459fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser467fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser513fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Trp622Ter Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Tyr613fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Cys643fs No assertion criteria intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gln527Ter No assertion criteria intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gln694Ter No assertion criteria intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Phe673del No assertion criteria CNOT3-related disorder

Pathogenic/Likely pathogenic 3

  • c.1904+2T>C Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Arg96Ter Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser245fs Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies

Likely pathogenic 26

  • p.Arg81Ser Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Thr86= Multiple submitters intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • c.2037+3A>C Single submitter Inborn genetic diseases
  • c.26-2A>G Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ala480fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Arg57Gly Single submitter CNOT3-related disorder
  • p.Arg735Leu Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Asn192Ser Single submitter
  • p.Gln40Arg Single submitter
  • p.Glu147Lys Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Gly9Arg Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.His699Tyr Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ile571del Single submitter
  • p.Leu747Pro Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Lys31= Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Lys50del Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Lys737Glu Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Met704Thr Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Met88Ile Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Pro314fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Pro395fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser365Ter Single submitter
  • p.Ser384fs Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser695fs Single submitter
  • p.Gln215Ter No assertion criteria Moyamoya angiopathy with developmental delay
  • p.Leu522Ile No assertion criteria Moyamoya angiopathy with developmental delay ⚠

Conflicting classifications of pathogenicity 18

  • p.Ala237Val Single submitter intellectual disability ⚠
  • p.Ala347Gly Single submitter Inborn genetic diseases ⚠
  • p.Ala347Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala536Pro Single submitter Inborn genetic diseases ⚠
  • p.Arg171Gln Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies ⚠
  • p.Arg188His Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies ⚠
  • p.Gln583Pro Single submitter Inborn genetic diseases ⚠
  • p.Glu174Lys Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies ⚠
  • p.Gly304Ser Single submitter complex neurodevelopmental disorder ⚠
  • p.Gly342Val Single submitter Inborn genetic diseases ⚠
  • p.Gly401Ser Single submitter ⚠
  • p.Gly402_Ser403insGlyGly Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.His313Tyr Single submitter Inborn genetic diseases ⚠
  • p.Pro328Leu Single submitter Inborn genetic diseases ⚠
  • p.Pro584= Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies
  • p.Ser104Asn Single submitter intellectual developmental disorder with speech delay, autism, and dysmorphic facies ⚠
  • p.Ser310Asn Single submitter Inborn genetic diseases ⚠
  • p.Thr134Met Single submitter Inborn genetic diseases ⚠

Benign 24

Benign/Likely benign 12

Likely benign 97

Uncertain significance 208