Is TRIM63 p.Arg62Trp (c.184C>T) pathogenic?

TRIM63 p.Arg62Trp (c.184C>T) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-27). AlphaMissense: ambiguous (0.4118); Ultra-rare (popmax 0.0166%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TRIM63 p.Arg62Trp (c.184C>T)?

TRIM63 p.Arg62Trp (c.184C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TRIM63 p.Arg62Trp (c.184C>T) in the general population?

TRIM63 p.Arg62Trp (c.184C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about TRIM63 p.Arg62Trp (c.184C>T)?

AlphaMissense predicts ambiguous (score 0.4118) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg62Trp

c.184C>T · rs148561702 · VCV2405233

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4118	ambiguous
REVEL	0.209	benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	25.8	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 0.0166% Middle Eastern · 1/6,040 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0068%

Overall 0.00686% 110/1,602,676 alleles · ultra-rare exomes 106/1,450,460 · genomes 4/152,216 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,040
European (non-Finnish)	0.00869%	11,506
Remaining individualsnot grpmax-eligible	0.00322%	31,022
East Asian	0.00224%	44,734
South Asian	0.00223%	44,806
Admixed American	0.00168%	59,370
African / African-American	0.00134%	74,788

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.Arg62Trp
Coding: c.184C>T
MANE Select: NM_032588
dbSNP: rs148561702
Type: single nucleotide variant
Location: chr1:26066416 (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.Arg62Gln Uncertain significance ★★ ⚠ same residue
TRIM63 p.Ala244Val 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-arg62trp (accessed [today's date]).

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