Is TRIM63 p.Trp59Arg (c.175T>C) pathogenic?

TRIM63 p.Trp59Arg (c.175T>C) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.6787); Rare (popmax 0.149%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TRIM63 p.Trp59Arg (c.175T>C)?

TRIM63 p.Trp59Arg (c.175T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TRIM63 p.Trp59Arg (c.175T>C) in the general population?

TRIM63 p.Trp59Arg (c.175T>C) is rare (popmax 0.149%, sas) (gnomAD).

What do computational predictors say about TRIM63 p.Trp59Arg (c.175T>C)?

AlphaMissense predicts likely pathogenic (score 0.6787) — an in-silico prediction, not a clinical call.

TRIM63 p.Trp59Arg

c.175T>C · rs561602133 · VCV3895209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6787	likely pathogenic
REVEL	0.079	moderately benign-leaning
SaProt	LLR -12.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	24.6	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 0.149% South Asian · 132/88,512 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.00848% 135/1,591,586 alleles · rare exomes 125/1,439,256 · genomes 10/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.149%	671
Remaining individualsnot grpmax-eligible	0.00325%	30,759
European (non-Finnish)	8.57e-05%	1,166,828

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: TRIM63
Protein: p.Trp59Arg
Coding: c.175T>C
MANE Select: NM_032588
dbSNP: rs561602133
Type: single nucleotide variant
Location: chr1:26066425 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB

Full TRIM63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRIM63 p.Ala244Val Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg62Trp Uncertain significance ★★ ⚠ same condition
TRIM63 c.855-1G>A Likely pathogenic ★ same condition
TRIM63 p.Ala48Val Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Cys145Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Cys23Tyr Uncertain significance ★ ⚠ same condition
TRIM63 p.Cys75Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Gln247Ter Conflicting classifications of pathogenicity ★ same condition

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/trim63-p-trp59arg (accessed [today's date]).

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