TRIP4 p.Ala398=
c.1194C>T · rs61738389 · VCV727406
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.12%, 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 · C>A here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.11 | GERP 1.9 |
| Overall | ||
| CADD | 8.842 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.12%
African / African-American · 841/74,998 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.03%
Overall
0.0599%
966/1,612,730 alleles · low-frequency
exomes 486/1,460,468 · genomes 480/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.12% | 89 |
| Remaining individualsnot grpmax-eligible | 0.0865% | 1,155 |
| Admixed American | 0.0517% | 1,935 |
| South Asian | 0.0187% | 5,353 |
| European (non-Finnish) | 0.00195% | 51,303 |
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.Ala398=
- Coding
- c.1194C>T
- MANE Select
- NM_016213
- dbSNP
- rs61738389
- Type
- single nucleotide variant
- Location
- chr15:64418564 (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 398
- an α-helix; the 'mediates interaction with ufl1' region
Similar variants
- TRIP4 p.Ala398Thr 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.Arg104Gln Uncertain significance ★★ ⚠ same type
- TRIP4 p.Arg189Cys 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-ala398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown