Is TRAP1 p.Ser488Arg (c.1462A>C) pathogenic?

TRAP1 p.Ser488Arg (c.1462A>C) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). AlphaMissense: ambiguous (0.3676); Very rare (popmax 0.00167%, amr).

How common is TRAP1 p.Ser488Arg (c.1462A>C) in the general population?

TRAP1 p.Ser488Arg (c.1462A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRAP1 p.Ser488Arg (c.1462A>C)?

AlphaMissense predicts ambiguous (score 0.3676) — an in-silico prediction, not a clinical call.

TRAP1 p.Ser488Arg

c.1462A>C · rs1192511571 · VCV2796848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3676	ambiguous
REVEL	0.272	benign-leaning
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.59	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	16.57	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 0.00167% Admixed American · 1/59,764 alleles

Overall 6.85e-05% 1/1,460,300 alleles · very rare

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.Ser488Arg
Coding: c.1462A>C
MANE Select: NM_016292
dbSNP: rs1192511571
Type: single nucleotide variant
Location: chr16:3664381 (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-ser488arg (accessed [today's date]).

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