TRIP12 p.Ser669=
c.2007C>T · VCV4960427
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 5.1 | GERP 0.14, phastCons 1 |
| Overall | ||
| CADD | 11.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,852 alleles
Overall
6.2e-05%
1/1,613,782 alleles · very rare
exomes 1/1,461,596 · genomes 0/152,186 · 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
- TRIP12
- Protein
- p.Ser669=
- Coding
- c.2007C>T
- MANE Select
- NM_001348323
- Type
- single nucleotide variant
- Location
- chr2:229811184 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 5 PDB
- Residue 669
- a UniProt-annotated variant site (in clabars; uncertain significance); an α-helix
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-ser669 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown