Sugi Variant

Sugi Variant/NR4A2

NR4A2 — 264 ClinVar variants

All ClinVar germline NR4A2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 125 flagged for review →

25 Pathogenic · 1 Pathogenic/Likely pathogenic · 26 Likely pathogenic · 5 Conflicting · 5 Benign · 2 Benign/Likely benign · 35 Likely benign · 165 Uncertain significance

Full NR4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 125

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 2

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 91

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

Predictors split 30

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

All NR4A2 variants

Pathogenic 25

  • c.1159-81_1540+67del Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • c.995-1G>A Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • c.-2-2del Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys299Phe Single submitter late-onset Parkinson disease
  • p.Cys299Ser Single submitter Inborn genetic diseases
  • p.Cys323Phe Single submitter
  • p.Gln154Ter Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Gln236Ter Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Gln5fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Gln96fs Single submitter
  • p.Leu198fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Lys179fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Met1fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Phe178fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Pro183fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Pro233fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ser11fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ser126Ter Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ser16fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ser27Ter Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ser59fs Single submitter
  • p.Arg319Gln No assertion criteria intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys280Tyr No assertion criteria intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys305Tyr No assertion criteria intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Pro201_Met202insTer No assertion criteria intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism

Pathogenic/Likely pathogenic 1

  • p.Gln109fs Multiple submitters intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism

Likely pathogenic 26

  • p.Ala270Val Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Arg312Trp Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Arg314Pro Single submitter
  • p.Arg341Gly Single submitter
  • p.Arg386delinsSerLeuAspTer Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Arg386Thr Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys263Trp Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys315Arg Single submitter Neurodevelopmental delay
  • p.Cys323Tyr Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Cys505Ter Single submitter Inborn genetic diseases
  • p.Gly285Asp Single submitter complex neurodevelopmental disorder
  • p.Gly285Val Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Ile500fs Single submitter
  • p.Leu462fs Single submitter
  • p.Lys288Arg Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Lys288Thr Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Phe320_Gln321delinsLeuTer Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Pro346Leu Single submitter NR4A2-related disorder
  • p.Ser125Cys Single submitter ⚠
  • p.Ser504Phe Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Tyr122del Single submitter
  • p.Val468fs Single submitter intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
  • p.Val469fs Single submitter Developmental disorder
  • c.1361+1G>A No assertion criteria NR4A2-related disorder
  • p.Pro201fs No assertion criteria autism spectrum disorder
  • p.Val307Gly No assertion criteria intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism

Conflicting classifications of pathogenicity 5

Benign 5

Benign/Likely benign 2

  • p.Ile163= Multiple submitters
  • p.Leu244= Multiple submitters late-onset Parkinson disease

Likely benign 35

Uncertain significance 165