TBX4 p.Pro288=
c.864G>A · rs1179957328 · VCV799376
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.1 |
| Overall | ||
| CADD | 0.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,010 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00155%
25/1,613,984 alleles · very rare
exomes 22/1,461,880 · genomes 3/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,002 |
| African / African-American | 0.00534% | 18,736 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| South Asian | 0.0022% | 45,528 |
| European (non-Finnish) | 0.00102% | 98,334 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- TBX4
- Protein
- p.Pro288=
- Coding
- c.864G>A
- MANE Select
- NM_001321120
- dbSNP
- rs1179957328
- Type
- single nucleotide variant
- Location
- chr17:61480162 (GRCh38)
- Gene constraint
- LOEUF 0.379 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.96
- Residue 288
- a UniProt-annotated variant site (in pappas; also responsible for ischiocoxopodopatellar syndrome in heterozygous carriers; no detectable protein expression in homozygous patient cells)
Similar variants
- TBX4 p.Pro288Ala Uncertain significance ★★ ⚠ same residue
- TBX4 p.Pro288Leu Uncertain significance ★ ⚠ same residue
- TBX4 c.1021+1G>A Pathogenic/Likely pathogenic ★★ same type
- TBX4 c.702+1G>A Pathogenic/Likely pathogenic ★★ same type
- TBX4 p.Arg250Trp Pathogenic ★★ same type
- TBX4 p.Arg261Ter Pathogenic ★★ same type
- TBX4 p.Arg340Ter Pathogenic/Likely pathogenic ★★ same type
- TBX4 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tbx4-p-pro288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown