Is TRAP1 p.Arg623His (c.1868G>A) pathogenic?

TRAP1 p.Arg623His (c.1868G>A) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.3896); Ultra-rare (popmax 0.0164%, mid).

How common is TRAP1 p.Arg623His (c.1868G>A) in the general population?

TRAP1 p.Arg623His (c.1868G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about TRAP1 p.Arg623His (c.1868G>A)?

AlphaMissense predicts ambiguous (score 0.3896) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg623His

c.1868G>A · VCV3460865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.3896	ambiguous
REVEL	0.622	indeterminate
SaProt	LLR -7.81	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	33.0	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00254% 41/1,613,316 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00801%	12,488
East Asian	0.00669%	14,955
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)	0.00246%	40,689
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Arg623His
Coding: c.1868G>A
MANE Select: NM_005223 · reported on NM_016292
Type: single nucleotide variant
Location: chr16:3662059 (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-arg623his (accessed [today's date]).

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