Is TRIM32 p.Ser174Phe (c.521C>T) pathogenic?

TRIM32 p.Ser174Phe (c.521C>T) is classified Conflicting classifications of pathogenicity in TRIM32 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2024-11-22). AlphaMissense: likely benign (0.2477); Ultra-rare (popmax 0.0352%, nfe); Associated with Bardet-Biedl syndrome 11.

What condition is associated with TRIM32 p.Ser174Phe (c.521C>T)?

TRIM32 p.Ser174Phe (c.521C>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.Ser174Phe (c.521C>T) in the general population?

TRIM32 p.Ser174Phe (c.521C>T) is ultra-rare (popmax 0.0352%, 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.Ser174Phe (c.521C>T)?

AlphaMissense predicts likely benign (score 0.2477) — an in-silico prediction, not a clinical call.

TRIM32 p.Ser174Phe

c.521C>T · rs138699534 · VCV288658

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.2477 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0352%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 11

Computational evidence

Protein change
AlphaMissense	0.2477	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -8.86	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	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	24.0	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 0.0352% European (non-Finnish) · 415/1,180,032 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.0271% 438/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0352%	2,843
Remaining individualsnot grpmax-eligible	0.016%	6,249
Admixed American	0.015%	6,667
African / African-American	0.004%	24,976
South Asian	0.0011%	91,082

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.Ser174Phe
Coding: c.521C>T
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs138699534
Type: single nucleotide variant
Location: chr9:116698263 (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-ser174phe (accessed [today's date]).

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