Is TRIM32 p.Gly287Cys (c.859G>T) pathogenic?

TRIM32 p.Gly287Cys (c.859G>T) is classified Uncertain significance in TRIM32 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-14). AlphaMissense: likely benign (0.2522); Very rare (popmax 0.00167%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2H.

How common is TRIM32 p.Gly287Cys (c.859G>T) in the general population?

TRIM32 p.Gly287Cys (c.859G>T) is very rare (popmax 0.00167%, amr) (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.Gly287Cys (c.859G>T)?

AlphaMissense predicts likely benign (score 0.2522) — an in-silico prediction, not a clinical call.

TRIM32 p.Gly287Cys

Q: What condition is associated with TRIM32 p.Gly287Cys (c.859G>T)?

TRIM32 p.Gly287Cys (c.859G>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2H, Bardet-Biedl syndrome 11 (ClinVar).

c.859G>T · VCV3596364

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2522 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2H

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2522	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	25.2	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 0.00167% Admixed American · 1/60,018 alleles

Overall 0.000124% 2/1,614,070 alleles · very rare exomes 2/1,461,772 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	8.47e-05%	1,180,034

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.Gly287Cys
Coding: c.859G>T
MANE Select: NM_012210
Type: single nucleotide variant
Location: chr9:116698601 (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-gly287cys (accessed [today's date]).

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