Is TRAP1 p.Glu89Val (c.266A>T) pathogenic?

TRAP1 p.Glu89Val (c.266A>T) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-03). AlphaMissense: ambiguous (0.3857); Ultra-rare (popmax 0.0334%, eas).

How common is TRAP1 p.Glu89Val (c.266A>T) in the general population?

TRAP1 p.Glu89Val (c.266A>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about TRAP1 p.Glu89Val (c.266A>T)?

AlphaMissense predicts ambiguous (score 0.3857) — an in-silico prediction, not a clinical call.

TRAP1 p.Glu89Val

c.266A>T · rs750282364 · VCV3181928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Computational evidence

Protein change
AlphaMissense	0.3857	ambiguous
REVEL	0.563	indeterminate
SaProt	LLR -8.59	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,874 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.000992% 16/1,613,526 alleles · ultra-rare exomes 12/1,461,390 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: TRAP1
Protein: p.Glu89Val
Coding: c.266A>T
MANE Select: NM_016292
dbSNP: rs750282364
Type: single nucleotide variant
Location: chr16:3689119 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB
Residue 89: a β-strand

Full TRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAP1 p.Ala319Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala409Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala50Ser Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala64Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala659Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala7Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg271Pro Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg340His 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/trap1-p-glu89val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown