Is TRAP1 p.Glu533= (c.1599G>A) pathogenic?

TRAP1 p.Glu533= (c.1599G>A) is classified Likely benign in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). Very rare (popmax 0.005%, amr).

How common is TRAP1 p.Glu533= (c.1599G>A) in the general population?

TRAP1 p.Glu533= (c.1599G>A) is very rare (popmax 0.005%, amr) (gnomAD).

TRAP1 p.Glu533=

c.1599G>A · VCV3712239

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.35	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -0.12	GERP -0.48, phastCons 0.52
Overall
CADD	8.903	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,006 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000496% 8/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,002
Remaining individualsnot grpmax-eligible	0.0048%	20,828
South Asian	0.0011%	91,080
European (non-Finnish)	8.47e-05%	1,180,020

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.Glu533=
Coding: c.1599G>A
MANE Select: NM_005223 · reported on NM_016292
Type: single nucleotide variant
Location: chr16:3663533 (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-glu533 (accessed [today's date]).

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