Is TRAP1 p.Arg495His (c.1484G>A) pathogenic?

TRAP1 p.Arg495His (c.1484G>A) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-16). AlphaMissense: ambiguous (0.3685); Ultra-rare (popmax 0.0351%, amr).

How common is TRAP1 p.Arg495His (c.1484G>A) in the general population?

TRAP1 p.Arg495His (c.1484G>A) is ultra-rare (popmax 0.0351%, amr) (gnomAD).

What do computational predictors say about TRAP1 p.Arg495His (c.1484G>A)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg495His

c.1484G>A · rs746111043 · VCV1308266

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, amr)

⚠ 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	0.3685	ambiguous
REVEL	0.454	indeterminate
SaProt	LLR -5.52	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, 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 0.0351% Admixed American · 21/59,746 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00521% 84/1,612,232 alleles · ultra-rare exomes 80/1,460,112 · genomes 4/152,120 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0351%	2,845
South Asian	0.0143%	6,982
European (non-Finnish)	0.00407%	24,570
Remaining individualsnot grpmax-eligible	0.00321%	31,201

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.Arg495His
Coding: c.1484G>A
MANE Select: NM_016292
dbSNP: rs746111043
Type: single nucleotide variant
Location: chr16:3664359 (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-arg495his (accessed [today's date]).

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