Sugi Variant

Sugi Variant/TBX4

TBX4 — 349 ClinVar variants

All ClinVar germline TBX4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 139 flagged for review →

28 Pathogenic · 9 Pathogenic/Likely pathogenic · 38 Likely pathogenic · 16 Conflicting · 41 Benign · 16 Benign/Likely benign · 48 Likely benign · 153 Uncertain significance

Full TBX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 139

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 9

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

Predictors lean, ClinVar uncertain 109

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

Predictors split 20

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

All TBX4 variants

Pathogenic 28

Pathogenic/Likely pathogenic 9

  • c.1021+1G>A Multiple submitters coxopodopatellar syndrome
  • c.702+1G>A Multiple submitters TBX4-related disorder
  • p.Arg340Ter Multiple submitters TBX4-related disorder
  • p.Arg353Ter Multiple submitters pulmonary hypertension, primary, 1
  • p.Asp329Tyr Multiple submitters TBX4-related disorder
  • p.Leu71fs Multiple submitters pulmonary hypertension, primary, 1
  • p.Phe224del Multiple submitters Pulmonary arterial hypertension associated with congenital heart disease
  • p.Pro372fs Multiple submitters pulmonary hypertension, primary, 1
  • p.Pro373fs Multiple submitters coxopodopatellar syndrome

Likely pathogenic 38

  • p.Tyr475fs Multiple submitters TBX4-related disorder
  • c.186+1G>A Single submitter coxopodopatellar syndrome
  • c.186+1G>T Single submitter
  • c.281+2T>A Single submitter
  • c.703-2A>G Single submitter
  • c.792-1G>C Single submitter pulmonary hypertension, primary, 1
  • p.Ala52fs Single submitter pulmonary hypertension, primary, 1
  • p.Arg250fs Single submitter TBX4-related disorder
  • p.Gln193Ter Single submitter pulmonary hypertension, primary, 1
  • p.Gln283fs Single submitter pulmonary hypertension, primary, 1
  • p.Gln465Ter Single submitter TBX4-related disorder
  • p.Glu306Ter Single submitter pulmonary hypertension, primary, 1
  • p.Glu61fs Single submitter pulmonary hypertension, primary, 1
  • p.Gly138fs Single submitter TBX4-related disorder
  • p.Gly49fs Single submitter pulmonary hypertension, primary, 1
  • p.Lys110fs Single submitter TBX4-related disorder
  • p.Lys191fs Single submitter pulmonary hypertension, primary, 1
  • p.Lys91Glu Single submitter coxopodopatellar syndrome
  • p.Met1Ile Single submitter coxopodopatellar syndrome
  • p.Pro180fs Single submitter Pulmonary arterial hypertension associated with congenital heart disease
  • p.Pro244fs Single submitter TBX4-related disorder
  • p.Pro47fs Single submitter TBX4-related disorder
  • p.Pro98Arg Single submitter Pulmonary arterial hypertension associated with congenital heart disease
  • p.Ser264fs Single submitter pulmonary hypertension, primary, 1
  • p.Ser311Ter Single submitter
  • p.Thr222fs Single submitter pulmonary hypertension, primary, 1
  • p.Trp421Ter Single submitter TBX4-related disorder
  • p.Tyr127Ser Single submitter pulmonary hypertension, primary, 1
  • p.Tyr192Ter Single submitter TBX4-related disorder
  • p.Tyr374Ter Single submitter pulmonary hypertension, primary, 1
  • p.Gln327Ter No assertion criteria coxopodopatellar syndrome
  • p.Gly41Ter No assertion criteria pulmonary arterial hypertension
  • p.His335fs No assertion criteria pulmonary arterial hypertension
  • p.Lys338Ter No assertion criteria pulmonary arterial hypertension
  • p.Phe14fs No assertion criteria pulmonary arterial hypertension
  • p.Thr296fs No assertion criteria pulmonary arterial hypertension
  • p.Thr326fs No assertion criteria pulmonary arterial hypertension
  • p.Thr388fs No assertion criteria pulmonary arterial hypertension

Conflicting classifications of pathogenicity 16

Benign 41

Benign/Likely benign 16

  • c.187-15C>T Multiple submitters coxopodopatellar syndrome
  • c.703-8C>T Multiple submitters coxopodopatellar syndrome
  • c.791+11G>A Multiple submitters coxopodopatellar syndrome
  • c.*7C>T Multiple submitters coxopodopatellar syndrome
  • p.Ala260= Multiple submitters
  • p.Ala35Val Multiple submitters coxopodopatellar syndrome
  • p.Asp53= Multiple submitters
  • p.Glu386= Multiple submitters coxopodopatellar syndrome
  • p.Glu541= Multiple submitters coxopodopatellar syndrome
  • p.Gly6Ser Multiple submitters coxopodopatellar syndrome
  • p.His335= Multiple submitters coxopodopatellar syndrome
  • p.Lys505= Multiple submitters coxopodopatellar syndrome
  • p.Ser406Cys Multiple submitters coxopodopatellar syndrome
  • p.Ser508= Multiple submitters coxopodopatellar syndrome
  • p.Ser8= Multiple submitters coxopodopatellar syndrome
  • p.Val362= Multiple submitters coxopodopatellar syndrome

Likely benign 48

Uncertain significance 153