Is TRAP1 p.Arg703Ter (c.2107C>T) pathogenic?

TRAP1 p.Arg703Ter (c.2107C>T) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-07). Ultra-rare (popmax 0.0356%, eas).

How common is TRAP1 p.Arg703Ter (c.2107C>T) in the general population?

TRAP1 p.Arg703Ter (c.2107C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

TRAP1 p.Arg703Ter

c.2107C>T · rs371020906 · VCV488976

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP -2.8, phastCons 0.29
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0356% East Asian · 16/44,886 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0138% 223/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
Admixed American	0.02%	5,001
African / African-American	0.0187%	5,358
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Finnishnot grpmax-eligible	0.0141%	7,107
European (non-Finnish)	0.013%	7,712
South Asian	0.00988%	10,118

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.Arg703Ter
Coding: c.2107C>T
MANE Select: NM_005223 · reported on NM_016292
dbSNP: rs371020906
Type: single nucleotide variant
Location: chr16:3658137 (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-arg703ter (accessed [today's date]).

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