Is TRAP1 p.Arg385Cys (c.1153C>T) pathogenic?

TRAP1 p.Arg385Cys (c.1153C>T) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: ambiguous (0.34); Very rare (popmax 0.00668%, afr).

How common is TRAP1 p.Arg385Cys (c.1153C>T) in the general population?

TRAP1 p.Arg385Cys (c.1153C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about TRAP1 p.Arg385Cys (c.1153C>T)?

AlphaMissense predicts ambiguous (score 0.34) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg385Cys

c.1153C>T · rs755371658 · VCV2371479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.34 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Computational evidence

Protein change
AlphaMissense	0.34	ambiguous
REVEL	0.631	indeterminate
SaProt	LLR -10.76	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, 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 0.00668% African / African-American · 5/74,838 alleles

Filtering AF 0.0052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00535% 86/1,608,596 alleles · very rare exomes 83/1,456,390 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,968
European (non-Finnish)	0.00637%	15,706
Remaining individualsnot grpmax-eligible	0.00482%	20,763
East Asian	0.00224%	44,656
Admixed American	0.00169%	59,332
South Asian	0.00111%	89,946

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.Arg385Cys
Coding: c.1153C>T
MANE Select: NM_016292
dbSNP: rs755371658
Type: single nucleotide variant
Location: chr16:3672712 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB

Full TRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAP1 p.Arg385His Uncertain significance ★ ⚠ same residue
TRAP1 p.Ala319Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala409Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala50Ser Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala64Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala659Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala7Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg271Pro Uncertain significance ★★ ⚠ same type

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-arg385cys (accessed [today's date]).

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