Is TRAP1 p.Ala617Val (c.1850C>T) pathogenic?

TRAP1 p.Ala617Val (c.1850C>T) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.6139); Ultra-rare (popmax 0.0146%, nfe).

How common is TRAP1 p.Ala617Val (c.1850C>T) in the general population?

TRAP1 p.Ala617Val (c.1850C>T) is ultra-rare (popmax 0.0146%, nfe) (gnomAD).

What do computational predictors say about TRAP1 p.Ala617Val (c.1850C>T)?

AlphaMissense predicts likely pathogenic (score 0.6139) — an in-silico prediction, not a clinical call.

TRAP1 p.Ala617Val

c.1850C>T · VCV4598606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0146%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6139	likely pathogenic
REVEL	0.291	indeterminate
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; 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	28.0	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 0.0146% European (non-Finnish) · 172/1,179,936 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0119% 192/1,613,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0146%	6,860
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,865
Remaining individualsnot grpmax-eligible	0.00961%	10,408
Finnishnot grpmax-eligible	0.00948%	10,553
Admixed American	0.00667%	14,998
African / African-American	0.00133%	74,938

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.Ala617Val
Coding: c.1850C>T
MANE Select: NM_005223 · reported on NM_016292
Type: single nucleotide variant
Location: chr16:3662077 (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-ala617val (accessed [today's date]).

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