Is TRIM63 p.Ser161fs (c.481_482del) pathogenic?

TRIM63 p.Ser161fs (c.481482del) is classified Pathogenic in TRIM63 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-24). Ultra-rare (popmax 0.0177%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Ser161fs (c.481_482del)?

TRIM63 p.Ser161fs (c.481_482del) is associated with Inborn genetic diseases, hypertrophic cardiomyopathy, cardiomyopathy, familial hypertrophic, 31 (ClinVar).

How common is TRIM63 p.Ser161fs (c.481_482del) in the general population?

TRIM63 p.Ser161fs (c.481_482del) is ultra-rare (popmax 0.0177%, nfe) (gnomAD).

TRIM63 p.Ser161fs

c.481_482del · rs540072010 · VCV985254

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, nfe)

Conditions

Inborn genetic diseases

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 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.6	GERP -4.5
Overall
CADD	34.0	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 0.0177% European (non-Finnish) · 209/1,179,960 alleles

Filtering AF 0.0157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.015%

Overall 0.0139% 225/1,613,958 alleles · ultra-rare exomes 220/1,461,704 · genomes 5/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0177%	5,646
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,919
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.00267%	37,509

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.Ser161fs
Coding: c.481_482del
MANE Select: NM_032588
dbSNP: rs540072010
Type: Microsatellite
Location: chr1:26061185 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 161: the 'interaction with ttn' region; a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy cardiomyopathy, familial hypertrophic, 31

Similar variants

TRIM63 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg183His Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg62Gln Uncertain significance ★★ ⚠ same condition
TRIM63 p.Arg79Cys Uncertain significance ★★ ⚠ same condition
TRIM63 p.Gln190Lys Uncertain significance ★★ ⚠ same condition
TRIM63 p.Pro113Leu Uncertain significance ★★ ⚠ same condition
TRIM63 p.Pro57Arg 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-ser161fs (accessed [today's date]).

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