Is TRIM32 p.Val95Ala (c.284T>C) pathogenic?

TRIM32 p.Val95Ala (c.284T>C) is classified Uncertain significance in TRIM32 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-17). AlphaMissense: likely benign (0.0932); Very rare (popmax 0.00924%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with TRIM32 p.Val95Ala (c.284T>C)?

TRIM32 p.Val95Ala (c.284T>C) is associated with Bardet-Biedl syndrome (ClinVar).

How common is TRIM32 p.Val95Ala (c.284T>C) in the general population?

TRIM32 p.Val95Ala (c.284T>C) is very rare (popmax 0.00924%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about TRIM32 p.Val95Ala (c.284T>C)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

TRIM32 p.Val95Ala

c.284T>C · rs780885702 · VCV1047448

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00924%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	18.89	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 0.00924% European (non-Finnish) · 109/1,180,040 alleles

Filtering AF 0.00782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00682% 110/1,613,936 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00924%	10,826
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Val95Ala
Coding: c.284T>C
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs780885702
Type: single nucleotide variant
Location: chr9:116698026 (GRCh38)

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

Disease context

Bardet-Biedl syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

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-val95ala (accessed [today's date]).

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