Sugi Variant

Sugi Variant/PNPLA1

PNPLA1 — 270 ClinVar variants

All ClinVar germline PNPLA1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 107 flagged for review →

19 Pathogenic · 8 Pathogenic/Likely pathogenic · 22 Likely pathogenic · 25 Conflicting · 38 Benign · 4 Benign/Likely benign · 41 Likely benign · 113 Uncertain significance

Full PNPLA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 107

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 9

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

Predictors lean, ClinVar uncertain 77

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

Predictors split 20

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

All PNPLA1 variants

Pathogenic 19

  • p.Ala434fs Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Asp172Asn Multiple submitters lamellar ichthyosis ⚠
  • p.Ser140Pro Multiple submitters PNPLA1-related disorder
  • c.439-2A>G Single submitter
  • p.Arg101Gly Single submitter lamellar ichthyosis
  • p.Arg440Ter Single submitter
  • p.Gln179Arg Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Pro295fs Single submitter
  • p.Pro92fs Single submitter
  • p.Ser19Leu Single submitter
  • p.Ser382fs Single submitter lamellar ichthyosis
  • p.Ser53Pro Single submitter lamellar ichthyosis
  • p.Tyr245del Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ala31Asp No assertion criteria Congenital ichthyosiform erythroderma
  • p.Ala59Val No assertion criteria autosomal recessive congenital ichthyosis 10
  • p.Cys150Arg No assertion criteria Congenital ichthyosiform erythroderma
  • p.Glu131Ter No assertion criteria autosomal recessive congenital ichthyosis 10
  • p.His121Pro No assertion criteria Congenital ichthyosiform erythroderma
  • p.Lys141Glu No assertion criteria autosomal recessive congenital ichthyosis 10

Pathogenic/Likely pathogenic 8

  • p.Ala34Pro Multiple submitters lamellar ichthyosis
  • p.Ala50Glu Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Arg298Ter Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Asp129Glu Multiple submitters Ichthyosis and erythrokeratoderma
  • p.Cys216Arg Multiple submitters lamellar ichthyosis ⚠
  • p.Pro163Leu Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Ser53Trp Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Ser112Tyr No assertion criteria autosomal recessive congenital ichthyosis 10

Likely pathogenic 22

  • p.Pro13fs Multiple submitters lamellar ichthyosis
  • p.Pro155Leu Multiple submitters lamellar ichthyosis
  • p.Ser53Leu Multiple submitters lamellar ichthyosis
  • c.1384+2T>C Single submitter autosomal recessive congenital ichthyosis 10
  • c.1469+1G>A Single submitter autosomal recessive congenital ichthyosis 10
  • c.206-1G>A Single submitter autosomal recessive congenital ichthyosis 10
  • c.504+2T>C Single submitter
  • c.715-2A>C Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ala34Thr Single submitter autosomal recessive congenital ichthyosis 10
  • p.Arg246Pro Single submitter autosomal recessive congenital ichthyosis 10
  • p.Arg246Ter Single submitter lamellar ichthyosis
  • p.Arg41fs Single submitter autosomal recessive congenital ichthyosis 10
  • p.Asn224Asp Single submitter Abnormality of the skin
  • p.Gln219Ter Single submitter autosomal recessive congenital ichthyosis 10
  • p.Gly30Arg Single submitter autosomal recessive congenital ichthyosis 10
  • p.Lys379fs Single submitter autosomal recessive congenital ichthyosis 10
  • p.Pro162Arg Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ser19Trp Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ser430Ter Single submitter autosomal recessive congenital ichthyosis 10
  • p.Tyr254fs Single submitter
  • p.Arg274fs No assertion criteria autosomal recessive congenital ichthyosis 10
  • p.Pro89Leu No assertion criteria autosomal recessive congenital ichthyosis 10

Conflicting classifications of pathogenicity 25

  • c.1469+10C>G Single submitter autosomal recessive congenital ichthyosis 10
  • c.205+5G>A Single submitter autosomal recessive congenital ichthyosis 10
  • c.439-6G>A Single submitter autosomal recessive congenital ichthyosis 10
  • c.439-7C>T Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ala29= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ala448Val Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Ala474Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala60Thr Single submitter Inborn genetic diseases ⚠
  • p.Arg106Gln Single submitter Inborn genetic diseases ⚠
  • p.Arg166Cys Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Gly433= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ile225= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ile271= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Leu124= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Leu443Ile Single submitter Inborn genetic diseases ⚠
  • p.Pro163Thr Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Pro205Leu Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Pro235Leu Single submitter ⚠
  • p.Pro354= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Pro92= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Ser53= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Thr128Met Single submitter autosomal recessive congenital ichthyosis 10 ⚠
  • p.Thr185= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Tyr248= Single submitter autosomal recessive congenital ichthyosis 10
  • p.Val531= Single submitter autosomal recessive congenital ichthyosis 10

Benign 38

Benign/Likely benign 4

  • p.Gln179= Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Glu288Gly Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.His209= Multiple submitters autosomal recessive congenital ichthyosis 10
  • p.Tyr488Ter Multiple submitters autosomal recessive congenital ichthyosis 10

Likely benign 41

Uncertain significance 113