Sugi Variant

Sugi Variant/HPDL

HPDL — 129 ClinVar variants

All ClinVar germline HPDL variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 66 flagged for review →

14 Pathogenic · 5 Pathogenic/Likely pathogenic · 28 Likely pathogenic · 5 Conflicting · 3 Benign · 14 Likely benign · 60 Uncertain significance

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

⚑ Evidence disagreements 66

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 5

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

Predictors agree, ClinVar conflicts 4

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

Predictors lean, ClinVar uncertain 44

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

Predictors split 13

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

All HPDL variants

Pathogenic 14

  • p.Gly50Asp Multiple submitters spastic paraplegia 83, autosomal recessive ⚠
  • p.Leu234fs Multiple submitters Inborn genetic diseases
  • p.Gln279Ter Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.His251Gln Single submitter ⚠
  • p.Leu338Pro Single submitter HPDL-related disorder
  • p.Leu55fs Single submitter Inborn genetic diseases
  • p.Pro254fs Single submitter Inborn genetic diseases
  • p.Pro264fs Single submitter Inborn genetic diseases
  • p.Ala115fs No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gly260Glu No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gly319fs No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Leu176Pro No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Trp179Cys No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Tyr118Ter No assertion criteria neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities

Pathogenic/Likely pathogenic 5

  • p.Gln32Ter Multiple submitters neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gly200fs Multiple submitters neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Met1Ile Multiple submitters Inborn genetic diseases
  • p.Ala86fs No assertion criteria Spastic paraplegia
  • p.Ile266Thr No assertion criteria Spastic paraplegia

Likely pathogenic 28

  • p.Thr263Met Multiple submitters neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities ⚠
  • p.Ala116fs Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Ala286fs Single submitter
  • p.Ala356Pro Single submitter spastic paraplegia 83, autosomal recessive
  • p.Ala78Thr Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities ⚠
  • p.Cys168Tyr Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gln243Ter Single submitter spastic paraplegia 83, autosomal recessive
  • p.Gln257fs Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gln342Ter Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
  • p.Gly185Cys Single submitter
  • p.Leu130fs Single submitter
  • p.Leu177fs Single submitter
  • p.Tyr288His Single submitter spastic paraplegia 83, autosomal recessive
  • p.Ala231Gly No assertion criteria Spastic paraplegia ⚠
  • p.Arg37Pro No assertion criteria Spastic paraplegia ⚠
  • p.Cys9Ter No assertion criteria Spastic paraplegia
  • p.Gln246Ter No assertion criteria
  • p.Glu268fs No assertion criteria
  • p.Gly140Arg No assertion criteria Spastic paraplegia
  • p.Leu217Pro No assertion criteria Spastic paraplegia
  • p.Ser173Tyr No assertion criteria Spastic paraplegia ⚠
  • p.Ser192Arg No assertion criteria ⚠
  • p.Thr165Pro No assertion criteria Spastic paraplegia
  • p.Thr175fs No assertion criteria Spastic paraplegia
  • p.Thr227fs No assertion criteria Spastic paraplegia
  • p.Thr263Arg No assertion criteria Spastic paraplegia
  • p.Thr332fs No assertion criteria Spastic paraplegia
  • p.Trp358Gly No assertion criteria Spastic paraplegia

Conflicting classifications of pathogenicity 5

  • p.Ala346fs Single submitter
  • p.Leu45Gln Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities ⚠
  • p.Pro190Leu Single submitter ⚠
  • p.Ser49Arg Single submitter spastic ataxia ⚠
  • p.Trp157Arg Single submitter neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities ⚠

Benign 3

Likely benign 14

Uncertain significance 60