Is TRAP1 p.His648= (c.1944C>T) pathogenic?

TRAP1 p.His648= (c.1944C>T) is classified Likely benign in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). Rare (popmax 0.185%, afr).

How common is TRAP1 p.His648= (c.1944C>T) in the general population?

TRAP1 p.His648= (c.1944C>T) is rare (popmax 0.185%, afr) (gnomAD).

TRAP1 p.His648=

c.1944C>T · rs137975630 · VCV2736616

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.185%, afr)

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
Constraint at this position
Conservation	phyloP 1.7	GERP -1.6, phastCons 0.92
Overall
CADD	3.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.185% African / African-American · 139/75,038 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.0121% 195/1,614,024 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.185%	540
Middle Eastern	0.033%	3,031
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.0208%	4,808
South Asian	0.00439%	22,770
European (non-Finnish)	0.00178%	56,190
Finnishnot grpmax-eligible	0.00156%	63,934

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.His648=
Coding: c.1944C>T
MANE Select: NM_005223 · reported on NM_016292
dbSNP: rs137975630
Type: single nucleotide variant
Location: chr16:3658862 (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-his648 (accessed [today's date]).

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