Sugi Variant

Sugi Variant/NOTCH2

NOTCH2 — 2193 ClinVar variants

All ClinVar germline NOTCH2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 1124 flagged for review →

54 Pathogenic · 4 Pathogenic/Likely pathogenic · 43 Likely pathogenic · 144 Conflicting · 80 Benign · 54 Benign/Likely benign · 612 Likely benign · 1202 Uncertain significance

Full NOTCH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 1124

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 3

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

Predictors agree, ClinVar conflicts 64

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

Predicted LoF vs a conflicting call 4

ClinVar submitters conflict, and it's a predicted loss-of-function change in a gene where LoF causes disease — flagged for review, not resolved (verify NMD-escape for C-terminal truncations). Non-missense.

Predictors lean, ClinVar uncertain 823

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 823

Predictors split 230

The independent predictors disagree with each other — read with care. · showing the 150 best-reviewed of 230

All NOTCH2 variants

Pathogenic 54

Pathogenic/Likely pathogenic 4

  • p.Arg2003Ter Multiple submitters Inborn genetic diseases
  • p.Gln2285Ter Multiple submitters acroosteolysis dominant type
  • p.Ile2304fs Multiple submitters acroosteolysis dominant type
  • p.Leu2135fs Multiple submitters NOTCH2-related disorder

Likely pathogenic 43

  • p.Glu1586fs Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Glu952fs Multiple submitters acroosteolysis dominant type
  • p.Val2151fs Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.1567+2T>G Single submitter
  • c.416-2A>G Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • c.5002+1G>A Single submitter acroosteolysis dominant type
  • c.5781+1G>T Single submitter acroosteolysis dominant type
  • c.6028-5T>A Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Ala1700fs Single submitter acroosteolysis dominant type
  • p.Ala2214fs Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Ala2356fs Single submitter acroosteolysis dominant type
  • p.Arg113Ter Single submitter acroosteolysis dominant type
  • p.Arg2047fs Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Arg91Ter Single submitter NOTCH2-related disorder
  • p.Asn2066fs Single submitter acroosteolysis dominant type
  • p.Asp437Ala Single submitter Alagille syndrome due to a NOTCH2 point mutation ⚠
  • p.Cys302fs Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Cys412Phe Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Cys498Arg Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Cys547Ser Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Gln2196Ter Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Gln2325Ter Single submitter acroosteolysis dominant type
  • p.Glu876Ter Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Gly1170Ter Single submitter acroosteolysis dominant type
  • p.Gly438Asp Single submitter
  • p.His267Gln Single submitter ⚠
  • p.His885fs Single submitter acroosteolysis dominant type
  • p.Leu2092fs Single submitter acroosteolysis dominant type
  • p.Lys1514Ter Single submitter acroosteolysis dominant type
  • p.Pro1810fs Single submitter NOTCH2-related disorder
  • p.Pro863Ser Single submitter Alagille syndrome due to a NOTCH2 point mutation ⚠
  • p.Ser1636Ter Single submitter NOTCH2-related disorder
  • p.Ser346_Cys347insTer Single submitter
  • p.Thr1808fs Single submitter
  • p.Tyr857fs Single submitter Alagille syndrome due to a NOTCH2 point mutation
  • p.Val2217fs Single submitter acroosteolysis dominant type
  • p.Val2305fs Single submitter acroosteolysis dominant type
  • c.3338-2A>G No assertion criteria Alagille syndrome due to a NOTCH2 point mutation
  • p.Gln1811Ter No assertion criteria Alagille syndrome due to a NOTCH2 point mutation
  • p.Gln2364Ter No assertion criteria NOTCH2-related disorder
  • p.Leu372fs No assertion criteria NOTCH2-related disorder
  • p.Phe2307fs No assertion criteria acroosteolysis dominant type
  • p.Ser2153_Leu2154insTer No assertion criteria Alagille syndrome due to a NOTCH2 point mutation

Conflicting classifications of pathogenicity 144

Benign 80

Benign/Likely benign 54

  • c.1108+14G>A Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.1567+12C>T Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.1568-17C>T Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.1681+9C>A Multiple submitters acroosteolysis dominant type
  • c.2026+6G>T Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.2480-4C>G Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.2599+12G>C Multiple submitters acroosteolysis dominant type
  • c.2752+17G>C Multiple submitters acroosteolysis dominant type
  • c.2981+11A>G Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • c.3655+54A>G Multiple submitters
  • c.-23C>A Multiple submitters
  • c.-31G>C Multiple submitters
  • p.Ala3Ser Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Ala439Thr Multiple submitters acroosteolysis dominant type
  • p.Ala862Val Multiple submitters acroosteolysis dominant type
  • p.Arg1251His Multiple submitters acroosteolysis dominant type
  • p.Arg1260His Multiple submitters acroosteolysis dominant type
  • p.Arg91Leu Multiple submitters acroosteolysis dominant type
  • p.Asn164Lys Multiple submitters Inborn genetic diseases
  • p.Asn1739= Multiple submitters acroosteolysis dominant type
  • p.Asn514Ser Multiple submitters acroosteolysis dominant type ⚠
  • p.Asp2362= Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Cys1173= Multiple submitters acroosteolysis dominant type
  • p.Cys1374= Multiple submitters acroosteolysis dominant type
  • p.Cys433= Multiple submitters acroosteolysis dominant type
  • p.Gln2308= Multiple submitters acroosteolysis dominant type
  • p.Gln466Lys Multiple submitters acroosteolysis dominant type
  • p.Glu1147= Multiple submitters acroosteolysis dominant type
  • p.Gly1169= Multiple submitters acroosteolysis dominant type
  • p.Gly1437= Multiple submitters acroosteolysis dominant type
  • p.His1160Arg Multiple submitters acroosteolysis dominant type ⚠
  • p.His2032Asn Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Ile1689Phe Multiple submitters acroosteolysis dominant type
  • p.Ile681Asn Multiple submitters acroosteolysis dominant type
  • p.Leu1012= Multiple submitters acroosteolysis dominant type
  • p.Leu1413His Multiple submitters acroosteolysis dominant type
  • p.Leu2348= Multiple submitters acroosteolysis dominant type
  • p.Leu2408His Multiple submitters acroosteolysis dominant type
  • p.Leu481= Multiple submitters acroosteolysis dominant type
  • p.Met1Ile Multiple submitters
  • p.Phe1209Val Multiple submitters acroosteolysis dominant type
  • p.Phe2015= Multiple submitters acroosteolysis dominant type
  • p.Pro2359Ala Multiple submitters acroosteolysis dominant type
  • p.Pro6fs Multiple submitters
  • p.Ser2162= Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Ser2172= Multiple submitters Alagille syndrome due to a NOTCH2 point mutation
  • p.Thr1039= Multiple submitters acroosteolysis dominant type
  • p.Thr145= Multiple submitters
  • p.Thr932= Multiple submitters acroosteolysis dominant type
  • p.Tyr2160Cys Multiple submitters acroosteolysis dominant type
  • p.Tyr825= Multiple submitters acroosteolysis dominant type
  • p.Val1667Ile Multiple submitters acroosteolysis dominant type
  • p.Val1667Phe Multiple submitters acroosteolysis dominant type
  • p.Val2075Met Multiple submitters acroosteolysis dominant type

Likely benign 612

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

Uncertain significance 1202

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