Is TRAP1 p.Ser482Arg (c.1444A>C) pathogenic?

TRAP1 p.Ser482Arg (c.1444A>C) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.9381); Very rare (popmax 0.00133%, afr).

How common is TRAP1 p.Ser482Arg (c.1444A>C) in the general population?

TRAP1 p.Ser482Arg (c.1444A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TRAP1 p.Ser482Arg (c.1444A>C)?

AlphaMissense predicts likely pathogenic (score 0.9381) — an in-silico prediction, not a clinical call.

TRAP1 p.Ser482Arg

c.1444A>C · VCV4830525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9381 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ 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	0.9381	likely pathogenic
REVEL	0.548	indeterminate
SaProt	LLR -14.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,008 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,612,388 alleles · very rare exomes 12/1,460,102 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,008
European (non-Finnish)	0.000933%	107,223

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.Ser482Arg
Coding: c.1444A>C
MANE Select: NM_016292
Type: single nucleotide variant
Location: chr16:3664399 (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-ser482arg (accessed [today's date]).

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