Is TRAP1 p.Arg128His (c.383G>A) pathogenic?

TRAP1 p.Arg128His (c.383G>A) is classified Benign/Likely benign in TRAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.1361); Low-frequency (popmax 1.73%, mid).

How common is TRAP1 p.Arg128His (c.383G>A) in the general population?

TRAP1 p.Arg128His (c.383G>A) is low-frequency (popmax 1.73%, mid) (gnomAD).

What do computational predictors say about TRAP1 p.Arg128His (c.383G>A)?

AlphaMissense predicts likely benign (score 0.1361) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg128His

c.383G>A · rs61758086 · VCV807977

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1361 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.73%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1361	likely benign
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -11.62	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	29.4	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 1.73% Middle Eastern · 105/6,060 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.36%

Overall 0.253% 4,088/1,614,088 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.73%	58
South Asian	1.16%	87
Remaining individualsnot grpmax-eligible	0.363%	275
Admixed American	0.227%	441
European (non-Finnish)	0.207%	483
Ashkenazi Jewishnot grpmax-eligible	0.138%	722
African / African-American	0.0893%	1,120
Finnishnot grpmax-eligible	0.0187%	5,336
East Asian	0.00668%	14,961

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.Arg128His
Coding: c.383G>A
MANE Select: NM_016292
dbSNP: rs61758086
Type: single nucleotide variant
Location: chr16:3686084 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB
Residue 128: an α-helix

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

Similar variants

TRAP1 p.Arg128Cys 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-arg128his (accessed [today's date]).

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