Is TRIM63 p.Lys238fs (c.713del) pathogenic?

TRIM63 p.Lys238fs (c.713del) is classified Likely pathogenic in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TRIM63 p.Lys238fs (c.713del)?

TRIM63 p.Lys238fs (c.713del) is associated with Cardiovascular phenotype (ClinVar).

How common is TRIM63 p.Lys238fs (c.713del) in the general population?

TRIM63 p.Lys238fs (c.713del) is very rare (popmax 0.000339%, nfe) (gnomAD).

TRIM63 p.Lys238fs

c.713del · VCV3895049

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.25	GERP -0.009, phastCons 0.98

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,162 alleles · very rare exomes 4/1,461,888 · genomes 0/152,274 · joint denominator

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.Lys238fs
Coding: c.713del
MANE Select: NM_032588
Type: Deletion
Location: chr1:26058508 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 238: 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.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-lys238fs (accessed [today's date]).

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