Is TRAP1 p.Asp684= (c.2052C>T) pathogenic?

TRAP1 p.Asp684= (c.2052C>T) is classified Benign in TRAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele.

TRAP1 p.Asp684=

Q: How common is TRAP1 p.Asp684= (c.2052C>T) in the general population?

TRAP1 p.Asp684= (c.2052C>T) is common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2052C>T · rs1059857 · VCV559145

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.8	GERP -3.5
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19% African / African-American · 14,263/74,914 alleles

Filtering AF 18.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.7%

Overall 5.37% 86,600/1,613,652 alleles · common exomes 73,606/1,461,602 · genomes 12,994/152,050 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19%	5
South Asian	9.66%	10
Finnishnot grpmax-eligible	6.43%	16
Remaining individualsnot grpmax-eligible	5.7%	18
East Asian	4.44%	23
Middle Eastern	4.36%	23
European (non-Finnish)	4.3%	23
Ashkenazi Jewishnot grpmax-eligible	3.51%	29
Amishnot grpmax-eligible	3.29%	30
Admixed American	3.07%	33

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.Asp684=
Coding: c.2052C>T
MANE Select: NM_016292
dbSNP: rs1059857
Type: single nucleotide variant
Location: chr16:3658192 (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-asp684 (accessed [today's date]).

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