Sugi Variant

Sugi Variant/IRF2BPL

IRF2BPL — 648 ClinVar variants

All ClinVar germline IRF2BPL variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 327 flagged for review →

37 Pathogenic · 11 Pathogenic/Likely pathogenic · 51 Likely pathogenic · 14 Conflicting · 12 Benign · 12 Benign/Likely benign · 164 Likely benign · 347 Uncertain significance

Full IRF2BPL gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 327

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 2

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.

Predicted LoF vs a conflicting call 3

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 182

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 182

Predictors split 136

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

All IRF2BPL variants

Pathogenic 37

  • p.Asn701fs Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln565Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln682Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Glu166Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala138fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala159fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala616fs Single submitter autism spectrum disorder
  • p.Ala94fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala97fs Single submitter
  • p.Gln103fs Single submitter
  • p.Gln123Ter Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln348fs Single submitter Inborn genetic diseases
  • p.Glu147Ter Single submitter
  • p.Glu461Ter Single submitter Inborn genetic diseases
  • p.Glu720fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gly150fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.His466Asp Single submitter ⚠
  • p.Leu713fs Single submitter
  • p.Phe64fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro174fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro200fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro272fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro596fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro685fs Single submitter Inborn genetic diseases
  • p.Pro706fs Single submitter Inborn genetic diseases
  • p.Ser318fs Single submitter intellectual disability
  • p.Thr316fs Single submitter Seizure
  • p.Trp368Ter Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Tyr173fs Single submitter
  • p.Ala321fs No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala92fs No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln124fs No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln126Ter No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Leu83fs No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Lys418Asn No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures ⚠
  • p.Pro372Arg No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures ⚠
  • p.Trp569Ter No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures

Pathogenic/Likely pathogenic 11

  • p.Ala708fs Multiple submitters IRF2BPL-related disorder
  • p.Ala95fs Multiple submitters IRF2BPL-related disorder
  • p.Arg188Ter Multiple submitters Inborn genetic diseases
  • p.Gln120Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln121Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln122Ter Multiple submitters IRF2BPL-related disorder
  • p.Gln167Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln497Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Glu172Ter Multiple submitters IRF2BPL-related disorder
  • p.Leu417fs Multiple submitters Inborn genetic diseases
  • p.Pro479Leu Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures ⚠

Likely pathogenic 51

  • p.Ala101fs Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln117Ter Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln119Ter Multiple submitters
  • p.Gly195fs Multiple submitters
  • p.Ala102fs Single submitter neurodevelopmental disorder
  • p.Ala162fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala96fs Single submitter
  • p.Arg391His Single submitter IRF2BPL-related disorder
  • p.Arg483His Single submitter
  • p.Arg68fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Asn197fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Asn255fs Single submitter IRF2BPL-related disorder
  • p.Asp395His Single submitter Global developmental delay
  • p.Asp704fs Single submitter IRF2BPL-related disorder
  • p.Cys714fs Single submitter neurodegenerative disease
  • p.Cys718fs Single submitter Inborn genetic diseases
  • p.Gln108fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln116fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln116Ter Single submitter Spastic paraplegia
  • p.Gln125Ter Single submitter
  • p.Gln127Ter Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln249Ter Single submitter IRF2BPL-related disorder
  • p.Gln777Ter Single submitter
  • p.Gly194fs Single submitter
  • p.Gly244fs Single submitter IRF2BPL-related disorder
  • p.Gly295fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gly400Ser Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.His736Asn Single submitter
  • p.Leu151fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Lys201Ter Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Lys394fs Single submitter IRF2BPL-related disorder
  • p.Lys418fs Single submitter
  • p.Lys543Ter Single submitter
  • p.Lys641Thr Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures ⚠
  • p.Phe420Ser Single submitter IRF2BPL-related disorder
  • p.Phe586fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro290fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro332fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Pro372Ala Single submitter IRF2BPL-related disorder ⚠
  • p.Pro667fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ser179_Leu180insThrArgHisArgArgTer Single submitter IRF2BPL-related disorder
  • p.Ser318Ter Single submitter
  • p.Ser360fs Single submitter IRF2BPL-related disorder
  • p.Thr237fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Thr425fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Trp471Ter Single submitter Inborn genetic diseases
  • p.Tyr431Ter Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Val81fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Arg391Cys No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln567Ter No assertion criteria IRF2BPL-related disorder
  • p.Thr386Met No assertion criteria neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures ⚠

Conflicting classifications of pathogenicity 14

Benign 12

  • p.Ala163= Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln107= Multiple submitters
  • p.Gln116= Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln126_Gln127del Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln127del Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Glu87= Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Tyr415= Multiple submitters neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Ala162_Ala164del Single submitter
  • p.Cys758= Single submitter
  • p.Gln123fs Single submitter neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • p.Gln127_Leu128insGlnGlnGlnGlnGlnGlnGln Single submitter
  • p.Ser769= Single submitter

Benign/Likely benign 12

Likely benign 164

Uncertain significance 347

Showing the top 300 by review status; the full set is in the sitemap.