Is TRAP1 p.Ala487Thr (c.1459G>A) pathogenic?

TRAP1 p.Ala487Thr (c.1459G>A) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-30). AlphaMissense: likely benign (0.0831); Very rare (popmax 0.00267%, afr).

How common is TRAP1 p.Ala487Thr (c.1459G>A) in the general population?

TRAP1 p.Ala487Thr (c.1459G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about TRAP1 p.Ala487Thr (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

TRAP1 p.Ala487Thr

c.1459G>A · rs368889500 · VCV2082413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 0.6, phastCons 0.97
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	16.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,611,898 alleles · very rare exomes 21/1,459,750 · genomes 3/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,444
European (non-Finnish)	0.00187%	53,607

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.Ala487Thr
Coding: c.1459G>A
MANE Select: NM_016292
dbSNP: rs368889500
Type: single nucleotide variant
Location: chr16:3664384 (GRCh38)

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

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-ala487thr (accessed [today's date]).

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