Is TRAP1 p.Arg495Cys (c.1483C>T) pathogenic?

TRAP1 p.Arg495Cys (c.1483C>T) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-19). AlphaMissense: ambiguous (0.4602); Very rare (popmax 0.00502%, amr).

How common is TRAP1 p.Arg495Cys (c.1483C>T) in the general population?

TRAP1 p.Arg495Cys (c.1483C>T) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about TRAP1 p.Arg495Cys (c.1483C>T)?

AlphaMissense predicts ambiguous (score 0.4602) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg495Cys

c.1483C>T · VCV3348712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, 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	0.4602	ambiguous
REVEL	0.426	indeterminate
SaProt	LLR -8.66	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	33.0	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 0.00502% Admixed American · 3/59,816 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00229% 37/1,612,878 alleles · very rare exomes 29/1,460,682 · genomes 8/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,939
African / African-American	0.00267%	37,456
European (non-Finnish)	0.00254%	39,321
East Asian	0.00223%	44,858
South Asian	0.0011%	90,842

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.Arg495Cys
Coding: c.1483C>T
MANE Select: NM_016292
Type: single nucleotide variant
Location: chr16:3664360 (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-arg495cys (accessed [today's date]).

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