Is TRAP1 p.Ala628Val (c.1883C>T) pathogenic?

TRAP1 p.Ala628Val (c.1883C>T) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.2352); Ultra-rare (popmax 0.0116%, nfe).

How common is TRAP1 p.Ala628Val (c.1883C>T) in the general population?

TRAP1 p.Ala628Val (c.1883C>T) is ultra-rare (popmax 0.0116%, nfe) (gnomAD).

What do computational predictors say about TRAP1 p.Ala628Val (c.1883C>T)?

AlphaMissense predicts likely benign (score 0.2352) — an in-silico prediction, not a clinical call.

TRAP1 p.Ala628Val

c.1883C>T · rs201211570 · VCV2359778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2352 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2352	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0116% European (non-Finnish) · 137/1,179,964 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00905% 146/1,613,228 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,613
East Asian	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0048%	20,824
African / African-American	0.00267%	37,470

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.Ala628Val
Coding: c.1883C>T
MANE Select: NM_005223 · reported on NM_016292
dbSNP: rs201211570
Type: single nucleotide variant
Location: chr16:3662044 (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-ala628val (accessed [today's date]).

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