TBX1 p.Pro337=
c.1011G>A · rs2517855315 · VCV2728699
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00266%, eas)
Conditions
1
DiGeorge syndrome
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 -2.1 | GERP -2.7 |
| Overall | ||
| CADD | 7.645 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00266%
East Asian · 1/37,536 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.00022%
3/1,363,600 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00266% | 37,536 |
| European (non-Finnish) | 0.000176% | 568,576 |
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
- TBX1
- Protein
- p.Pro337=
- Coding
- c.1011G>A
- MANE Select
- NM_001379200
- dbSNP
- rs2517855315
- Type
- single nucleotide variant
- Location
- chr22:19765977 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.12 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.15 · 1 PDB
- Residue 337
- a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)
Similar variants
- TBX1 p.Pro337Leu Uncertain significance ★★ ⚠ same residue
- TBX1 c.711+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TBX1 p.Ala21Thr Likely pathogenic ★★ same condition
- TBX1 p.Gln355Ter Pathogenic/Likely pathogenic ★★ same condition
- TBX1 p.Glu408Ter Pathogenic/Likely pathogenic ★★ same condition
- TBX1 c.1036+5G>A Uncertain significance ★★ same condition
- TBX1 c.34+6C>T Uncertain significance ★★ same condition
- TBX1 c.438-5C>A Uncertain significance ★★ same condition
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/tbx1-p-pro337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown