Sugi Variant

Sugi Variant/SMPD4

SMPD4 — 261 ClinVar variants

All ClinVar germline SMPD4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 156 flagged for review →

9 Pathogenic · 3 Pathogenic/Likely pathogenic · 19 Likely pathogenic · 7 Conflicting · 7 Benign · 1 Benign/Likely benign · 47 Likely benign · 168 Uncertain significance

Full SMPD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 156

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 agree, ClinVar conflicts 3

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

Predictors lean, ClinVar uncertain 126

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

Predictors split 27

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

All SMPD4 variants

Pathogenic 9

  • c.345+1G>T Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.270-1G>A Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.792+2T>G Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.-43del Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.-67_-66del Single submitter Inborn genetic diseases
  • p.Gln422Ter Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Ile496fs Single submitter
  • c.1453+1G>A No assertion criteria neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Leu453fs No assertion criteria neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Pathogenic/Likely pathogenic 3

  • c.1290-9G>A Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Arg502Ter Multiple submitters
  • p.Leu262fs Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Likely pathogenic 19

  • c.1098-2A>G Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.127-2A>G Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.1660-28_1666del Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.1893+2T>C Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Ala183fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Asp658fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Asp690fs Single submitter
  • p.Gln28Ter Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Gln483fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Gln538Ter Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Gln688fs Single submitter
  • p.Glu692Ter Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Glu85Ter Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Leu192Pro Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Leu68fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Lys654fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Pro92fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Ser748fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Tyr184fs Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Conflicting classifications of pathogenicity 7

  • c.270-8G>A Single submitter
  • p.Ala392fs Single submitter Abnormal cerebral morphology
  • p.Ala635Val Single submitter Inborn genetic diseases ⚠
  • p.Arg190= Single submitter
  • p.Phe380del Single submitter Abnormal cerebral morphology
  • p.Pro407Leu Single submitter neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies ⚠
  • p.Val64Ile Single submitter Inborn genetic diseases ⚠

Benign 7

  • c.1097+27A>G Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.2025+45C>T Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.345+33G>A Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • p.Ala761= Multiple submitters
  • p.Thr245= Multiple submitters neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
  • c.-106C>A Single submitter ⚠
  • p.Ser586= No assertion criteria

Benign/Likely benign 1

Likely benign 47

Uncertain significance 168