Is TRIM63 p.Gln247Ter (c.739C>T) pathogenic?

TRIM63 p.Gln247Ter (c.739C>T) is classified Conflicting classifications of pathogenicity in TRIM63 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2024-10-10). Ultra-rare (popmax 0.066%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TRIM63 p.Gln247Ter (c.739C>T)?

TRIM63 p.Gln247Ter (c.739C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy, familial hypertrophic cardiomyopathy (ClinVar).

How common is TRIM63 p.Gln247Ter (c.739C>T) in the general population?

TRIM63 p.Gln247Ter (c.739C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

TRIM63 p.Gln247Ter

c.739C>T · rs148395034 · VCV222849

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,060 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0507% 818/1,614,210 alleles · ultra-rare exomes 734/1,461,892 · genomes 84/152,318 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.723%	138
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Middle Easterngrpmax	0.066%	1,515
Finnishnot grpmax-eligible	0.0656%	1,525
Admixed American	0.0566%	1,766
European (non-Finnish)	0.0394%	2,538
South Asian	0.00439%	22,772
African / African-American	0.00267%	37,521

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln247Ter
Coding: c.739C>T
MANE Select: NM_032588
dbSNP: rs148395034
Type: single nucleotide variant
Location: chr1:26058482 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 247: a UniProt-annotated variant site (in cmh31; likely pathogenic; no protein detected in patient cells; loss of function in protein ubiquitination); 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

Also linked: hypertrophic cardiomyopathy familial hypertrophic cardiomyopathy cardiomyopathy, familial hypertrophic, 31

Similar variants

TRIM63 p.Ala244Val Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg62Trp Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg74His Uncertain significance ★★ ⚠ same condition
TRIM63 c.855-1G>A Likely pathogenic ★ same condition
TRIM63 c.1051+1G>A Uncertain significance ★ same condition
TRIM63 p.Ala48Val Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Arg74Cys 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-gln247ter (accessed [today's date]).

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