Sugi Variant

Sugi Variant/UCHL1

UCHL1 — 236 ClinVar variants

All ClinVar germline UCHL1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 60 flagged for review →

12 Pathogenic · 3 Pathogenic/Likely pathogenic · 10 Likely pathogenic · 6 Conflicting · 18 Benign · 8 Benign/Likely benign · 86 Likely benign · 93 Uncertain significance

Full UCHL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 60

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 1

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

Predicted LoF vs a conflicting call 1

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 44

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

Predictors split 14

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

All UCHL1 variants

Pathogenic 12

  • p.Asn88fs Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Gln116Ter Single submitter
  • p.Gln140Ter Single submitter
  • p.Gln84Ter Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Glu11fs Single submitter
  • p.Glu7Ala Single submitter early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • p.Gly24fs Single submitter optic nerve disorder
  • p.Lys123fs Single submitter UCHL1-related disorder
  • p.Thr121fs Single submitter optic nerve disorder
  • p.Ala216Asp No assertion criteria early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • p.Gln25Ter No assertion criteria spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Leu34fs No assertion criteria spastic paraplegia 79A, autosomal dominant, with ataxia

Pathogenic/Likely pathogenic 3

  • p.Arg178Ter Multiple submitters spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Gln58Ter Multiple submitters spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Phe117fs Multiple submitters UCHL1-related disorder

Likely pathogenic 10

  • c.325+1G>A Single submitter early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • c.44_45+2del Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia
  • c.459+1dup Single submitter UCHL1-related disorder
  • c.459+2T>C Single submitter early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • c.460-2A>G Single submitter
  • p.Ala130fs Single submitter
  • p.Asp191fs Single submitter UCHL1-related disorder
  • p.Gly210del Single submitter early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • p.Lys195Ter Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Asn9fs No assertion criteria UCHL1-related disorder

Conflicting classifications of pathogenicity 6

  • c.34-8C>G Single submitter
  • c.412-4G>A Single submitter Parkinson disease 5, autosomal dominant, susceptibility to
  • p.Arg153Trp Single submitter Parkinson disease 5, autosomal dominant, susceptibility to
  • p.Leu52_Phe53insLeu Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia
  • p.Met124Leu Single submitter Parkinson disease 5, autosomal dominant, susceptibility to ⚠
  • p.Val22fs Single submitter spastic paraplegia 79A, autosomal dominant, with ataxia ⚠

Benign 18

Benign/Likely benign 8

  • c.175-5C>T Multiple submitters Parkinson disease 5, autosomal dominant, susceptibility to
  • c.326-4del Multiple submitters early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
  • c.326-5_326-4dup Multiple submitters
  • c.34-19C>T Multiple submitters
  • c.45+19C>A Multiple submitters
  • c.45+6T>C Multiple submitters Parkinson disease 5, autosomal dominant, susceptibility to
  • p.Glu203= Multiple submitters Parkinson disease 5, autosomal dominant, susceptibility to
  • p.Gly186= Multiple submitters Parkinson disease 5, autosomal dominant, susceptibility to

Likely benign 86

Uncertain significance 93