Is TRAP1 p.Arg469His (c.1406G>A) pathogenic?

TRAP1 p.Arg469His (c.1406G>A) is classified Benign/Likely benign in TRAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.1988); Rare (popmax 0.83%, nfe); Associated with congenital anomaly of kidney and urinary tract.

What condition is associated with TRAP1 p.Arg469His (c.1406G>A)?

TRAP1 p.Arg469His (c.1406G>A) is associated with congenital anomaly of kidney and urinary tract (ClinVar).

How common is TRAP1 p.Arg469His (c.1406G>A) in the general population?

TRAP1 p.Arg469His (c.1406G>A) is rare (popmax 0.83%, nfe) (gnomAD).

What do computational predictors say about TRAP1 p.Arg469His (c.1406G>A)?

AlphaMissense predicts likely benign (score 0.1988) — an in-silico prediction, not a clinical call.

TRAP1 p.Arg469His

c.1406G>A · rs144787542 · VCV559147

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1988 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.83%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital anomaly of kidney and urinary tract

Computational evidence

Protein change
AlphaMissense	0.1988	likely benign
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -11.96	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	28.6	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 0.83% European (non-Finnish) · 9,786/1,179,226 alleles

Filtering AF 0.816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.81%

Overall 0.708% 11,408/1,611,828 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.09%	92
European (non-Finnish)grpmax	0.83%	121
Remaining individualsnot grpmax-eligible	0.662%	151
South Asian	0.275%	364
Admixed American	0.232%	432
Middle Eastern	0.231%	432
Ashkenazi Jewishnot grpmax-eligible	0.112%	894
African / African-American	0.107%	937
East Asian	0.00223%	44,838

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg469His
Coding: c.1406G>A
MANE Select: NM_005223 · reported on NM_016292
dbSNP: rs144787542
Type: single nucleotide variant
Location: chr16:3664437 (GRCh38)

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

Disease context

congenital anomaly of kidney and urinary tract — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg469his (accessed [today's date]).

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