TBX4 p.Pro152=
c.456G>T · rs375043323 · VCV3001877
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -5.7 |
| Overall | ||
| CADD | 11.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,880 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00105%
17/1,614,164 alleles · ultra-rare
exomes 17/1,461,856 · genomes 0/152,308 · joint denominator
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.Pro152=
- Coding
- c.456G>T
- MANE Select
- NM_001321120
- dbSNP
- rs375043323
- Type
- single nucleotide variant
- Location
- chr17:61467564 (GRCh38)
- Gene constraint
- LOEUF 0.379 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.96
- Residue 152
- a DNA-binding region; 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.Pro152Leu 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
- TBX4 p.Arg527Ter 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-pro152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown