Is TRIM32 p.Pro137Ser (c.409C>T) pathogenic?

TRIM32 p.Pro137Ser (c.409C>T) is classified Conflicting classifications of pathogenicity in TRIM32 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0791); Rare (popmax 0.263%, eas); Associated with Bardet-Biedl syndrome 11.

What condition is associated with TRIM32 p.Pro137Ser (c.409C>T)?

TRIM32 p.Pro137Ser (c.409C>T) is associated with Bardet-Biedl syndrome 11, autosomal recessive limb-girdle muscular dystrophy type 2H, Bardet-Biedl syndrome (ClinVar).

How common is TRIM32 p.Pro137Ser (c.409C>T) in the general population?

TRIM32 p.Pro137Ser (c.409C>T) is rare (popmax 0.263%, eas) (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.Pro137Ser (c.409C>T)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

TRIM32 p.Pro137Ser

c.409C>T · rs200997003 · VCV364717

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.263%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 11

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.8	phastCons 0.94
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	17.83	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

Grpmax group 0.263% East Asian · 118/44,842 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.21%

Overall 0.00905% 146/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.263%	380
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0217%	4,618
South Asian	0.0011%	91,080

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.Pro137Ser
Coding: c.409C>T
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs200997003
Type: single nucleotide variant
Location: chr9:116698151 (GRCh38)

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

Disease context

Bardet-Biedl syndrome 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-pro137ser (accessed [today's date]).

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