Is TRIM32 p.Arg563Cys (c.1687C>T) pathogenic?

TRIM32 p.Arg563Cys (c.1687C>T) is classified Uncertain significance in TRIM32 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-17). AlphaMissense: likely benign (0.3369); Very rare (popmax 0.00133%, afr); Associated with TRIM32-related disorder.

What condition is associated with TRIM32 p.Arg563Cys (c.1687C>T)?

TRIM32 p.Arg563Cys (c.1687C>T) is associated with TRIM32-related disorder, Bardet-Biedl syndrome (ClinVar).

How common is TRIM32 p.Arg563Cys (c.1687C>T) in the general population?

TRIM32 p.Arg563Cys (c.1687C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TRIM32 p.Arg563Cys (c.1687C>T)?

AlphaMissense predicts likely benign (score 0.3369) — an in-silico prediction, not a clinical call.

TRIM32 p.Arg563Cys

c.1687C>T · rs1274265404 · VCV2050686

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

TRIM32-related disorder

Computational evidence

Protein change
AlphaMissense	0.3369	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -9.23	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 4.9	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,958 bp · p 0.00073 · regional, not allelic
Overall
CADD	26.4	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 0.00133% African / African-American · 1/75,028 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,028
European (non-Finnish)	0.000593%	168,576

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.Arg563Cys
Coding: c.1687C>T
MANE Select: NM_001365068 · reported on NM_012210
dbSNP: rs1274265404
Type: single nucleotide variant
Location: chr9:116699429 (GRCh38)

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

Disease context

TRIM32-related disorder

Also linked: Bardet-Biedl syndrome

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-arg563cys (accessed [today's date]).

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