TRIP12 p.Pro2041=
c.6123G>A · rs747909233 · VCV3045557
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0283%, amr)
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 0.07 | GERP -1.1, phastCons 0.9 |
| Overall | ||
| CADD | 13.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0283%
Admixed American · 17/59,994 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00366%
59/1,613,954 alleles · ultra-rare
exomes 57/1,461,808 · genomes 2/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0283% | 3,529 |
| South Asian | 0.0231% | 4,336 |
| African / African-American | 0.004% | 24,969 |
| European (non-Finnish) | 0.00153% | 65,555 |
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.Pro2041=
- Coding
- c.6123G>A
- MANE Select
- NM_001348323
- dbSNP
- rs747909233
- Type
- single nucleotide variant
- Location
- chr2:229767635 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 5 PDB
- Residue 2041
- a UniProt-annotated variant site (in clabars; uncertain significance); a UniProt-annotated variant site (in clabars); the hect domain
Similar variants
- TRIP12 p.Pro2041Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro2041 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown