Is TRAP1 p.Arg491Trp (c.1471C>T) pathogenic?

TRAP1 p.Arg491Trp (c.1471C>T) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1323); Ultra-rare (popmax 0.0165%, mid).

How common is TRAP1 p.Arg491Trp (c.1471C>T) in the general population?

TRAP1 p.Arg491Trp (c.1471C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TRAP1 p.Arg491Trp (c.1471C>T)?

AlphaMissense predicts likely benign (score 0.1323) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg491Trp

c.1471C>T · rs370076676 · VCV2079374

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1323 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 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	0.1323	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -12.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP -0.53, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	25.2	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 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000992% 16/1,612,480 alleles · ultra-rare exomes 14/1,460,284 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
African / African-American	0.004%	24,969
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
South Asian	0.0022%	45,400
Remaining individualsnot grpmax-eligible	0.0016%	62,390
European (non-Finnish)	0.000678%	147,435

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.Arg491Trp
Coding: c.1471C>T
MANE Select: NM_016292
dbSNP: rs370076676
Type: single nucleotide variant
Location: chr16:3664372 (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-arg491trp (accessed [today's date]).

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