Is TRAP1 p.Arg692His (c.2075G>A) pathogenic?

TRAP1 p.Arg692His (c.2075G>A) is classified Benign in TRAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1188); Low-frequency (popmax 4.11%, nfe).

How common is TRAP1 p.Arg692His (c.2075G>A) in the general population?

TRAP1 p.Arg692His (c.2075G>A) is low-frequency (popmax 4.11%, nfe) (gnomAD).

What do computational predictors say about TRAP1 p.Arg692His (c.2075G>A)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg692His

c.2075G>A · rs2791 · VCV559144

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.11%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP -0.63, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	21.2	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 4.11% European (non-Finnish) · 48,444/1,179,818 alleles

Filtering AF 4.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.06%

Overall 3.56% 57,502/1,613,862 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.59%	18
European (non-Finnish)grpmax	4.11%	24
Admixed American	3.69%	27
Remaining individualsnot grpmax-eligible	3.3%	30
Finnishnot grpmax-eligible	3.23%	31
Middle Eastern	1.98%	51
South Asian	1.87%	53
Ashkenazi Jewishnot grpmax-eligible	1.08%	93
African / African-American	0.648%	154
East Asian	0.0802%	1,247

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg692His
Coding: c.2075G>A
MANE Select: NM_005223 · reported on NM_016292
dbSNP: rs2791
Type: single nucleotide variant
Location: chr16:3658169 (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-arg692his (accessed [today's date]).

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