TRIP4 p.Pro503=
c.1509G>A · rs367621867 · VCV2158508
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.036%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.19 | GERP -3.5, phastCons 0.31 |
| Overall | ||
| CADD | 11.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.036%
African / African-American · 27/74,904 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0219%
Overall
0.00329%
53/1,611,946 alleles · ultra-rare
exomes 34/1,459,690 · genomes 19/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.036% | 2,774 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,803 |
| Admixed American | 0.0117% | 8,512 |
| East Asian | 0.0067% | 14,921 |
| South Asian | 0.00331% | 30,167 |
| European (non-Finnish) | 0.000424% | 235,849 |
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
- TRIP4
- Protein
- p.Pro503=
- Coding
- c.1509G>A
- MANE Select
- NM_016213
- dbSNP
- rs367621867
- Type
- single nucleotide variant
- Location
- chr15:64425565 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.54 · 10 PDB
- Residue 503
- the asch domain
Similar variants
- TRIP4 p.Pro503Leu Uncertain significance ★ ⚠ same residue
- TRIP4 p.Pro503Ser Uncertain significance ★ ⚠ same residue
- TRIP4 c.272-1G>T Likely pathogenic ★★ same type
- TRIP4 p.Arg309Ter Pathogenic/Likely pathogenic ★★ same type
- TRIP4 p.Arg466Ter Pathogenic/Likely pathogenic ★★ same type
- TRIP4 p.Leu20Ter Pathogenic ★★ same type
- TRIP4 p.Trp297Ter Pathogenic ★★ same type
- TRIP4 p.Ala398Thr 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/trip4-p-pro503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown