Is TRAP1 p.Arg271Pro (c.812G>C) pathogenic?

TRAP1 p.Arg271Pro (c.812G>C) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.7055); Ultra-rare (popmax 0.0339%, mid).

How common is TRAP1 p.Arg271Pro (c.812G>C) in the general population?

TRAP1 p.Arg271Pro (c.812G>C) is ultra-rare (popmax 0.0339%, mid) (gnomAD).

What do computational predictors say about TRAP1 p.Arg271Pro (c.812G>C)?

AlphaMissense predicts likely pathogenic (score 0.7055) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg271Pro

c.812G>C · rs201753276 · VCV1921450

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7055	likely pathogenic
REVEL	0.589	indeterminate
SaProt	LLR -15.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -0.59, phastCons 0.23
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	20.4	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 0.0339% Middle Eastern · 2/5,900 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00161% 26/1,612,410 alleles · ultra-rare exomes 20/1,460,220 · genomes 6/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0339%	2,950
African / African-American	0.00935%	10,697
Remaining individualsnot grpmax-eligible	0.00481%	20,804
European (non-Finnish)	0.0011%	90,714
South Asian	0.0011%	90,828

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.Arg271Pro
Coding: c.812G>C
MANE Select: NM_016292
dbSNP: rs201753276
Type: single nucleotide variant
Location: chr16:3676038 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB
Residue 271: an α-helix

Full TRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAP1 p.Arg271Gln Uncertain significance ★ ⚠ same residue
TRAP1 p.Ala319Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala409Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala50Ser Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala64Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala659Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala7Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg340His Uncertain significance ★★ ⚠ same type

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-arg271pro (accessed [today's date]).

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