TRIP12 p.Pro877=
c.2631G>A · VCV4533686
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.424%, 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 4.2 | GERP 0.15, phastCons 1 |
| Overall | ||
| CADD | 14.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.424%
African / African-American · 317/74,806 alleles
Filtering AF
0.385%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.37%
Overall
0.0279%
446/1,597,692 alleles · rare
exomes 246/1,445,472 · genomes 200/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.424% | 236 |
| Middle Eastern | 0.15% | 668 |
| Remaining individualsnot grpmax-eligible | 0.034% | 2,939 |
| Admixed American | 0.015% | 6,649 |
| European (non-Finnish) | 0.00762% | 13,116 |
| South Asian | 0.00111% | 89,730 |
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
- TRIP12
- Protein
- p.Pro877=
- Coding
- c.2631G>A
- MANE Select
- NM_001348323
- Type
- single nucleotide variant
- Location
- chr2:229805749 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 5 PDB
- Residue 877
- the 'disordered' region; a UniProt-annotated variant site (in clabars; uncertain significance); the wwe domain
Similar variants
- TRIP12 c.3624+1G>A Likely pathogenic ★★ same type
- TRIP12 p.Arg1635Gln Pathogenic/Likely pathogenic ★★ same type
- TRIP12 p.Arg1635Ter Pathogenic/Likely pathogenic ★★ same type
- TRIP12 p.Arg551Ter Pathogenic ★★ same type
- TRIP12 p.Gln338Ter Pathogenic ★★ same type
- TRIP12 p.Gln689Ter Pathogenic ★★ same type
- TRIP12 c.4215+4A>G Uncertain significance ★★ same type
- TRIP12 p.Ala1042Val 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/trip12-p-pro877 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown