Is TRIM63 p.Pro113Leu (c.338C>T) pathogenic?

TRIM63 p.Pro113Leu (c.338C>T) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1815); Ultra-rare (popmax 0.0432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Pro113Leu (c.338C>T)?

TRIM63 p.Pro113Leu (c.338C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Pro113Leu (c.338C>T) in the general population?

TRIM63 p.Pro113Leu (c.338C>T) is ultra-rare (popmax 0.0432%, nfe) (gnomAD).

What do computational predictors say about TRIM63 p.Pro113Leu (c.338C>T)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

TRIM63 p.Pro113Leu

c.338C>T · rs199936688 · VCV2353439

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0432%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	28.7	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 0.0432% European (non-Finnish) · 510/1,179,940 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0388%

Overall 0.0344% 555/1,613,814 alleles · ultra-rare exomes 523/1,461,640 · genomes 32/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0432%	2,314
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Admixed American	0.0183%	5,454
African / African-American	0.0147%	6,810
East Asian	0.00223%	44,896
South Asian	0.0011%	91,076

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.Pro113Leu
Coding: c.338C>T
MANE Select: NM_032588
dbSNP: rs199936688
Type: single nucleotide variant
Location: chr1:26061329 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 113: the 'interaction with ttn' region

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

Similar variants

TRIM63 p.Pro113= Likely benign ★ same residue
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.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-pro113leu (accessed [today's date]).

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