Is TRIM32 p.Pro653Ser (c.1957C>T) pathogenic?

TRIM32 p.Pro653Ser (c.1957C>T) is classified Uncertain significance in TRIM32 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-24). AlphaMissense: likely benign (0.1547); Very rare (popmax 0.0022%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with TRIM32 p.Pro653Ser (c.1957C>T)?

TRIM32 p.Pro653Ser (c.1957C>T) is associated with Bardet-Biedl syndrome, autosomal recessive limb-girdle muscular dystrophy type 2H, Bardet-Biedl syndrome 11 (ClinVar).

How common is TRIM32 p.Pro653Ser (c.1957C>T) in the general population?

TRIM32 p.Pro653Ser (c.1957C>T) is very rare (popmax 0.0022%, 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.Pro653Ser (c.1957C>T)?

AlphaMissense predicts likely benign (score 0.1547) — an in-silico prediction, not a clinical call.

TRIM32 p.Pro653Ser

c.1957C>T · rs899549661 · VCV598557

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.1547	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -5.13	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 7.7	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	24.7	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 0.0022% European (non-Finnish) · 26/1,180,052 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,614,078 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.Pro653Ser
Coding: c.1957C>T
MANE Select: NM_012210
dbSNP: rs899549661
Type: single nucleotide variant
Location: chr9:116699699 (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

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

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-pro653ser (accessed [today's date]).

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