Is TRIM32 p.Val504Leu (c.1510G>T) pathogenic?

TRIM32 p.Val504Leu (c.1510G>T) is classified Uncertain significance in TRIM32 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-12). AlphaMissense: likely benign (0.3018); Very rare (popmax 0.0011%, sas); Associated with Bardet-Biedl syndrome.

What condition is associated with TRIM32 p.Val504Leu (c.1510G>T)?

TRIM32 p.Val504Leu (c.1510G>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is TRIM32 p.Val504Leu (c.1510G>T) in the general population?

TRIM32 p.Val504Leu (c.1510G>T) is very rare (popmax 0.0011%, sas) (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.Val504Leu (c.1510G>T)?

AlphaMissense predicts likely benign (score 0.3018) — an in-silico prediction, not a clinical call.

TRIM32 p.Val504Leu

c.1510G>T · rs1165772522 · VCV1432537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.3018	likely benign
REVEL	0.536	indeterminate
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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	24.3	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 0.0011% South Asian · 1/91,090 alleles

Overall 6.84e-05% 1/1,461,894 alleles · very rare

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.Val504Leu
Coding: c.1510G>T
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs1165772522
Type: single nucleotide variant
Location: chr9:116699252 (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-val504leu (accessed [today's date]).

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