TBX2 p.Pro53=
c.159C>G · VCV4936313
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -4.3 |
| Overall | ||
| CADD | 11.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 1/22,794 alleles
Overall
0.0002%
2/998,818 alleles · very rare
exomes 2/852,108 · genomes 0/146,710 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,794 |
| European (non-Finnish) | 0.000119% | 840,781 |
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.Pro53=
- Coding
- c.159C>G
- MANE Select
- NM_005994
- Type
- single nucleotide variant
- Location
- chr17:61400335 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.13
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-pro53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown