Is TRIM63 p.Ala244Val (c.731C>T) pathogenic?

TRIM63 p.Ala244Val (c.731C>T) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0986); Ultra-rare (popmax 0.0495%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TRIM63 p.Ala244Val (c.731C>T)?

TRIM63 p.Ala244Val (c.731C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TRIM63 p.Ala244Val (c.731C>T) in the general population?

TRIM63 p.Ala244Val (c.731C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about TRIM63 p.Ala244Val (c.731C>T)?

AlphaMissense predicts likely benign (score 0.0986) — an in-silico prediction, not a clinical call.

TRIM63 p.Ala244Val

c.731C>T · rs755534853 · VCV3328873

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0986	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.055, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	21.1	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00285% 46/1,614,208 alleles · ultra-rare exomes 40/1,461,890 · genomes 6/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Admixed American	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00237%	42,144
South Asian	0.0011%	91,084

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.Ala244Val
Coding: c.731C>T
MANE Select: NM_032588
dbSNP: rs755534853
Type: single nucleotide variant
Location: chr1:26058490 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 244: an α-helix

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.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
TRIM63 p.Gly11Ala Uncertain significance ★ ⚠ 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-ala244val (accessed [today's date]).

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