TRIP12 p.Pro708=
c.2124A>G · rs145741062 · VCV1711528
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.726%, mid)
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 0.27 | GERP -0.73, phastCons 1 |
| Overall | ||
| CADD | 9.121 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.726%
Middle Eastern · 44/6,060 alleles
Filtering AF
0.556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.496%
Overall
0.177%
2,857/1,614,050 alleles · rare
exomes 2,684/1,461,796 · genomes 173/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.726% | 138 |
| South Asian | 0.486% | 206 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| Remaining individualsnot grpmax-eligible | 0.232% | 431 |
| Ashkenazi Jewishnot grpmax-eligible | 0.216% | 463 |
| European (non-Finnish) | 0.172% | 580 |
| Admixed American | 0.158% | 632 |
| African / African-American | 0.0227% | 4,413 |
| Finnishnot grpmax-eligible | 0.0187% | 5,334 |
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.Pro708=
- Coding
- c.2124A>G
- MANE Select
- NM_001348323
- dbSNP
- rs145741062
- Type
- single nucleotide variant
- Location
- chr2:229810977 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 5 PDB
- Residue 708
- a UniProt-annotated variant site (in clabars; uncertain significance)
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-pro708 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown