TBX2 p.Pro393=
c.1179C>T · rs189227009 · VCV732390
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.57%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.6 | GERP -4.2 |
| Overall | ||
| CADD | 2.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.57%
African / African-American · 1,153/73,536 alleles
Filtering AF
1.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.46%
Overall
0.083%
1,284/1,546,548 alleles · low-frequency
exomes 582/1,394,196 · genomes 702/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.57% | 64 |
| Admixed American | 0.11% | 913 |
| Remaining individualsnot grpmax-eligible | 0.0963% | 1,038 |
| Middle Eastern | 0.0205% | 4,872 |
| South Asian | 0.00828% | 12,073 |
| European (non-Finnish) | 0.000694% | 144,113 |
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
- TBX2
- Protein
- p.Pro393=
- Coding
- c.1179C>T
- MANE Select
- NM_005994
- dbSNP
- rs189227009
- Type
- single nucleotide variant
- Location
- chr17:61405329 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.13
- Residue 393
- the 'disordered' region
Similar variants
- TBX2 p.Arg20Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- TBX2 p.Ala374Thr Uncertain significance ★★ ⚠ same type
- TBX2 p.Arg185His Uncertain significance ★★ ⚠ same type
- TBX2 p.Arg616Trp Uncertain significance ★★ ⚠ same type
- TBX2 p.Gly536Arg Uncertain significance ★★ same type
- TBX2 p.Leu304Val Uncertain significance ★★ ⚠ same type
- TBX2 p.Lys148Gln Uncertain significance ★★ ⚠ same type
- TBX2 p.Pro39Gln Uncertain significance ★★ ⚠ 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/tbx2-p-pro393 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown