TBX2 p.Pro44=
c.132G>C · VCV4936310
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000113%, nfe)
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 1.4 | GERP -4.5, phastCons 1 |
| Overall | ||
| CADD | 13.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000113%
European (non-Finnish) · 1/884,664 alleles
Overall
9.2e-05%
1/1,086,796 alleles · very rare
exomes 1/940,228 · genomes 0/146,568 · 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
- TBX2
- Protein
- p.Pro44=
- Coding
- c.132G>C
- MANE Select
- NM_005994
- Type
- single nucleotide variant
- Location
- chr17:61400308 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.13
Similar variants
- TBX2 p.Pro44Gln Uncertain significance ★★ same residue
- 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
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-pro44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown