Is TRIM32 p.Pro288Arg (c.863C>G) pathogenic?

TRIM32 p.Pro288Arg (c.863C>G) is classified Uncertain significance in TRIM32 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.2231); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2H.

How common is TRIM32 p.Pro288Arg (c.863C>G) in the general population?

TRIM32 p.Pro288Arg (c.863C>G) is absent from gnomAD v4.1 (gnomAD).

How is TRIM32-related limb-girdle muscular dystrophy R8 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TRIM32 p.Pro288Arg (c.863C>G)?

AlphaMissense predicts likely benign (score 0.2231) — an in-silico prediction, not a clinical call.

TRIM32 p.Pro288Arg

Q: What condition is associated with TRIM32 p.Pro288Arg (c.863C>G)?

TRIM32 p.Pro288Arg (c.863C>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2H, Bardet-Biedl syndrome 11 (ClinVar).

c.863C>G · VCV3596365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2H

Computational evidence

Protein change
AlphaMissense	0.2231	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -0.17	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRIM32
Protein: p.Pro288Arg
Coding: c.863C>G
MANE Select: NM_001365068 · reported on NM_012210
Type: single nucleotide variant
Location: chr9:116698605 (GRCh38)

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2H — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 11

For TRIM32-related limb-girdle muscular dystrophy R8 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

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-pro288arg (accessed [today's date]).

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