Sugi Variant

Sugi Variant/ENPP1

ENPP1 — 941 ClinVar variants

All ClinVar germline ENPP1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 337 flagged for review →

53 Pathogenic · 9 Pathogenic/Likely pathogenic · 37 Likely pathogenic · 58 Conflicting · 126 Benign · 13 Benign/Likely benign · 226 Likely benign · 419 Uncertain significance

Full ENPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 337

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 6

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

Predictors agree, ClinVar conflicts 26

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

Predictors lean, ClinVar uncertain 259

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 259

Predictors split 46

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

All ENPP1 variants

Pathogenic 53

  • c.2230+1G>A Multiple submitters arterial calcification, generalized, of infancy, 1
  • p.Arg476Ter Multiple submitters hypophosphatemic rickets, autosomal recessive, 2
  • p.Arg782Ter Multiple submitters ENPP1-related disorder
  • p.Asn731fs Multiple submitters hypophosphatemic rickets, autosomal recessive, 2
  • p.Glu192fs Multiple submitters hypophosphatemic rickets, autosomal recessive, 2
  • p.Glu893Ter Multiple submitters hypophosphatemic rickets, autosomal recessive, 2
  • p.Lys905fs Multiple submitters ENPP1-related disorder
  • p.Pro305Thr Multiple submitters ENPP1-related disorder
  • p.Tyr261Ter Multiple submitters ENPP1-related disorder
  • c.(1091+1_1092-1 Single submitter arterial calcification, generalized, of infancy, 1
  • c.1273+1G>A Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.1273+2T>C Single submitter arterial calcification, generalized, of infancy, 1
  • c.1437+1G>C Single submitter
  • c.1437+1G>T Single submitter
  • c.2101-2A>T Single submitter arterial calcification, generalized, of infancy, 1
  • c.2444+702_*868del Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.430+1del Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.915+1G>A Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Ala66fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Arg888Trp Single submitter
  • p.Asn446fs Single submitter
  • p.Cys177Arg Single submitter
  • p.Gln744Ter Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Gln767fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Glu2Ter Single submitter
  • p.Gly266Arg Single submitter arterial calcification, generalized, of infancy, 1
  • p.Gly266Val Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Gly751fs Single submitter
  • p.Gly96_Leu97insTer Single submitter
  • p.Ile336fs Single submitter
  • p.Ile889fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Leu572fs Single submitter
  • p.Leu810fs Single submitter
  • p.Leu914Ter Single submitter arterial calcification, generalized, of infancy, 1
  • p.Lys171Ter Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Lys70Ter Single submitter arterial calcification, generalized, of infancy, 1
  • p.Lys816Ter Single submitter
  • p.Pro365fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Ser100fs Single submitter ENPP1-related disorder
  • p.Ser343Ter Single submitter
  • p.Ser750fs Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Trp356Ter Single submitter Coronary sclerosis, medial, of infancy
  • p.Tyr312Ter Single submitter ENPP1-related disorder
  • c.2230+5G>A No assertion criteria arterial calcification, generalized, of infancy, 1
  • p.Asp538His No assertion criteria arterial calcification, generalized, of infancy, 1
  • p.Cys149Ser No assertion criteria hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Cys164Ser No assertion criteria hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Cys177Tyr No assertion criteria hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Gln358fs No assertion criteria arterial calcification, generalized, of infancy, 1
  • p.Gly186Arg No assertion criteria arterial calcification, generalized, of infancy, 1 ⚠
  • p.Lys293fs No assertion criteria arterial calcification, generalized, of infancy, 1
  • p.Tyr371Phe No assertion criteria arterial calcification, generalized, of infancy, 1
  • p.Tyr901Ser No assertion criteria hypophosphatemic rickets, autosomal recessive, 2

Pathogenic/Likely pathogenic 9

  • c.313+1G>A Multiple submitters hypopigmentation-punctate palmoplantar keratoderma syndrome
  • c.715+1G>C Multiple submitters
  • p.Arg456Ter Multiple submitters type 2 diabetes mellitus
  • p.Arg481Trp Multiple submitters hypophosphatemic rickets, autosomal recessive, 2 ⚠
  • p.Gly10fs Multiple submitters ENPP1-related disorder
  • p.Gly342Val Multiple submitters Coronary sclerosis, medial, of infancy ⚠
  • p.Gly586Arg Multiple submitters Autosomal recessive ENPP1-related disorders
  • p.Trp877Ter Multiple submitters hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Tyr471Cys Multiple submitters ENPP1-related disorder ⚠

Likely pathogenic 37

  • c.2608-1G>A Multiple submitters hypophosphatemic rickets, autosomal recessive, 2
  • p.Glu866Lys Multiple submitters hypopigmentation-punctate palmoplantar keratoderma syndrome
  • c.1092-2A>C Single submitter
  • c.1165-1G>T Single submitter
  • c.1565+1G>T Single submitter type 2 diabetes mellitus
  • c.1724-1G>T Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.2312-1G>A Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • c.2312-5_2313del Single submitter
  • c.556+2T>G Single submitter ENPP1-related disorder
  • c.795+1G>A Single submitter arterial calcification, generalized, of infancy, 1
  • c.796-2A>G Single submitter
  • p.Arg888Gln Single submitter ⚠
  • p.Asp135fs Single submitter ENPP1-related disorder
  • p.Asp42fs Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Cys108Phe Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Cys120Ser Single submitter
  • p.Cys126Ter Single submitter
  • p.Cys176Arg Single submitter ENPP1-related disorder
  • p.Gln676Ter Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Glu2fs Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Glu409fs Single submitter
  • p.Leu579Phe Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Leu611fs Single submitter ENPP1-related disorder
  • p.Met1Arg Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Phe257fs Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Phe501fs Single submitter
  • p.Pro334Ala Single submitter arterial calcification, generalized, of infancy, 1
  • p.Pro828fs Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Thr245fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Thr254fs Single submitter
  • p.Thr916fs Single submitter arterial calcification, generalized, of infancy, 1
  • p.Trp190Cys Single submitter arterial calcification, generalized, of infancy, 1
  • p.Trp356Arg Single submitter arterial calcification, generalized, of infancy, 1
  • p.Tyr244Ter Single submitter ENPP1-related disorder
  • p.Tyr570Cys Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Val396fs Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Ile567fs No assertion criteria ENPP1-related disorder

Conflicting classifications of pathogenicity 58

  • c.1164+9A>G Single submitter arterial calcification, generalized, of infancy, 1
  • c.1566-15A>G Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • c.2230+13C>T Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.2444+10T>C Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.313+10del Single submitter
  • c.313+10T>G Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.313+11G>T Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.313+13G>T Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.313+15G>T Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • c.313+8_313+9insTTGTGT Single submitter
  • c.313+9_313+10insGGTG Single submitter
  • c.313+9GT[22] Single submitter arterial calcification, generalized, of infancy, 1
  • c.313+9GT[23] Single submitter
  • c.-10C>T Single submitter arterial calcification, generalized, of infancy, 1
  • c.-13G>A Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Ala352= Single submitter arterial calcification, generalized, of infancy, 1
  • p.Arg12Gly Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome ⚠
  • p.Arg774Cys Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Arg774His Single submitter Inborn genetic diseases ⚠
  • p.Arg782Gln Single submitter Inborn genetic diseases ⚠
  • p.Arg821His Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Arg886Thr Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Asn179Ser Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Asn597= Single submitter arterial calcification, generalized, of infancy, 1
  • p.Asn746His Single submitter ENPP1-related disorder ⚠
  • p.Asn792Lys Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Asn792Ser Single submitter hypophosphatemic rickets, autosomal recessive, 2 ⚠
  • p.Asp175Asn Single submitter Inborn genetic diseases ⚠
  • p.Cys195Arg Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Gln666= Single submitter arterial calcification, generalized, of infancy, 1
  • p.Gly56= Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Gly738Arg Single submitter ENPP1-related disorder ⚠
  • p.Gly751Glu Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Gly805= Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Gly9= Single submitter
  • p.His654Gln Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome ⚠
  • p.His777Arg Single submitter hypophosphatemic rickets, autosomal recessive, 2 ⚠
  • p.Leu514= Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Leu522= Single submitter
  • p.Leu579Val Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Leu611Val Single submitter hypophosphatemic rickets ⚠
  • p.Lys173Gln Single submitter inherited obesity ⚠
  • p.Pro250Leu Single submitter ENPP1-related disorder ⚠
  • p.Pro52Ser Single submitter hypophosphatemic rickets, autosomal recessive, 2 ⚠
  • p.Pro581= Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Pro919= Single submitter hypophosphatemic rickets, autosomal recessive, 2
  • p.Ser287Phe Single submitter ⚠
  • p.Ser590Asn Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Ser875= Single submitter hypopigmentation-punctate palmoplantar keratoderma syndrome
  • p.Ser875Phe Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Ser876Leu Single submitter Inborn genetic diseases ⚠
  • p.Thr696= Single submitter
  • p.Thr705Met Single submitter type 2 diabetes mellitus ⚠
  • p.Thr779Asn Single submitter hypophosphatemic rickets, autosomal recessive, 2 ⚠
  • p.Tyr451Cys Single submitter arterial calcification, generalized, of infancy, 1 ⚠
  • p.Tyr513Cys Single submitter ⚠
  • p.Tyr551= Single submitter arterial calcification, generalized, of infancy, 1
  • p.Tyr551Cys Single submitter arterial calcification, generalized, of infancy, 1 ⚠

Benign 126

Benign/Likely benign 13

Likely benign 226

Uncertain significance 419

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