Is TRIM32 p.Arg147Gln (c.440G>A) pathogenic?

TRIM32 p.Arg147Gln (c.440G>A) is classified Uncertain significance in TRIM32 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0798); Very rare (popmax 0.00533%, afr); Associated with TRIM32-related disorder.

What condition is associated with TRIM32 p.Arg147Gln (c.440G>A)?

TRIM32 p.Arg147Gln (c.440G>A) is associated with TRIM32-related disorder, autosomal recessive limb-girdle muscular dystrophy type 2H, Bardet-Biedl syndrome 11 (ClinVar).

How common is TRIM32 p.Arg147Gln (c.440G>A) in the general population?

TRIM32 p.Arg147Gln (c.440G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about TRIM32 p.Arg147Gln (c.440G>A)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

TRIM32 p.Arg147Gln

c.440G>A · rs552938001 · VCV462948

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TRIM32-related disorder

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.8	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,052 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00273% 44/1,614,126 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,763
South Asian	0.00439%	22,770
Admixed American	0.00333%	30,005
European (non-Finnish)	0.0028%	35,759
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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: TRIM32
Protein: p.Arg147Gln
Coding: c.440G>A
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs552938001
Type: single nucleotide variant
Location: chr9:116698182 (GRCh38)

Full TRIM32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRIM32-related disorder

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2H Bardet-Biedl syndrome 11 Bardet-Biedl syndrome

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/trim32-p-arg147gln (accessed [today's date]).

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