Sugi Variant

Sugi Variant/TBR1

TBR1 — 336 ClinVar variants

All ClinVar germline TBR1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 183 flagged for review →

26 Pathogenic · 8 Pathogenic/Likely pathogenic · 38 Likely pathogenic · 7 Conflicting · 4 Benign · 51 Likely benign · 202 Uncertain significance

Full TBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 183

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 6

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 134

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

Predictors split 42

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

All TBR1 variants

Pathogenic 26

  • p.Asp66fs Multiple submitters intellectual developmental disorder with autism and speech delay
  • c.1128+2T>C Single submitter
  • c.969+1G>C Single submitter intellectual developmental disorder with autism and speech delay
  • p.Ala578fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Asn313fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Asp376His Single submitter intellectual developmental disorder with autism and speech delay ⚠
  • p.Gln323Ter Single submitter
  • p.Glu223Gln Single submitter Inborn genetic diseases
  • p.Gly128fs Single submitter neurodevelopmental disorder
  • p.Ile139fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Ile55fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Pro455fs Single submitter
  • p.Ser417Ter Single submitter intellectual developmental disorder with autism and speech delay
  • p.Thr408fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Thr56fs Single submitter Inborn genetic diseases
  • p.Trp545Ter Single submitter intellectual developmental disorder with autism and speech delay
  • p.Tyr169Ter Single submitter intellectual developmental disorder with autism and speech delay
  • p.Tyr553fs Single submitter
  • c.1190+2T>G No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Ala136fs No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Asn374His No assertion criteria intellectual developmental disorder with autism and speech delay ⚠
  • p.Lys228Glu No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Lys389Glu No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Thr350_Ser351insTer No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Thr378Ser No assertion criteria intellectual developmental disorder with autism and speech delay
  • p.Trp271Cys No assertion criteria intellectual developmental disorder with autism and speech delay

Pathogenic/Likely pathogenic 8

  • c.1190+1G>A Multiple submitters TBR1-related disorder
  • p.Arg392Trp Multiple submitters intellectual developmental disorder with autism and speech delay
  • p.Gln282Ter Multiple submitters Moderate global developmental delay
  • p.Gln373Arg Multiple submitters Moderate global developmental delay
  • p.Ser238fs Multiple submitters Moderate global developmental delay
  • p.Thr457fs Multiple submitters Moderate global developmental delay
  • p.Trp271Arg Multiple submitters Severe global developmental delay
  • p.Trp299Ter Multiple submitters Marfanoid habitus and intellectual disability

Likely pathogenic 38

  • c.(1128+1_1129-1 Single submitter intellectual developmental disorder with autism and speech delay
  • c.692+2T>C Single submitter intellectual developmental disorder with autism and speech delay
  • p.Ala156_Tyr157insTer Single submitter Moderate global developmental delay
  • p.Ala388Pro Single submitter intellectual developmental disorder with autism and speech delay
  • p.Arg231Gly Single submitter intellectual developmental disorder with autism and speech delay
  • p.Arg424fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Arg574fs Single submitter Inborn genetic diseases
  • p.Asn385Asp Single submitter
  • p.Asp245delinsValTrpPheTer Single submitter Inborn genetic diseases
  • p.Asp349Gly Single submitter TBR1-related disorder
  • p.Asp393fs Single submitter Moderate global developmental delay
  • p.Asp413His Single submitter ⚠
  • p.Gln167Ter Single submitter intellectual developmental disorder with autism and speech delay
  • p.Gln185Ter Single submitter attention deficit-hyperactivity disorder
  • p.Gln191Ter Single submitter
  • p.Gln352Ter Single submitter
  • p.Gln552fs Single submitter Severe global developmental delay
  • p.Gly390Arg Single submitter intellectual developmental disorder with autism and speech delay
  • p.His338Pro Single submitter intellectual developmental disorder with autism and speech delay
  • p.Ile225Phe Single submitter Severe global developmental delay
  • p.Leu213His Single submitter Inborn genetic diseases
  • p.Leu237Ter Single submitter
  • p.Leu7fs Single submitter
  • p.Lys216Ter Single submitter intellectual developmental disorder with autism and speech delay
  • p.Phe253fs Single submitter TBR1-related disorder
  • p.Pro453fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Pro550fs Single submitter Severe global developmental delay
  • p.Pro551fs Single submitter intellectual developmental disorder with autism and speech delay
  • p.Ser549fs Single submitter Delayed fine motor development
  • p.Thr312fs Single submitter attention deficit-hyperactivity disorder
  • p.Thr312Lys Single submitter
  • p.Trp264Cys Single submitter
  • p.Trp271Ser Single submitter Moderate global developmental delay
  • p.Tyr176fs Single submitter TBR1-related disorder
  • p.Tyr679fs Single submitter
  • p.Val369_Ala371del Single submitter Limb myoclonus
  • c.970-3C>G No assertion criteria TBR1-related disorder
  • p.Cys402Ter No assertion criteria intellectual developmental disorder with autism and speech delay

Conflicting classifications of pathogenicity 7

Benign 4

  • c.*10G>A Multiple submitters History of neurodevelopmental disorder
  • p.Leu18= Multiple submitters Inborn genetic diseases
  • p.Thr378= Multiple submitters intellectual developmental disorder with autism and speech delay
  • p.Gly452_Pro453insAlaGly Single submitter Inborn genetic diseases

Likely benign 51

Uncertain significance 202