Is TRIM63 p.Gln229Pro (c.686A>C) pathogenic?

TRIM63 p.Gln229Pro (c.686A>C) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely pathogenic (0.6279); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Gln229Pro (c.686A>C)?

TRIM63 p.Gln229Pro (c.686A>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Gln229Pro (c.686A>C) in the general population?

TRIM63 p.Gln229Pro (c.686A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRIM63 p.Gln229Pro (c.686A>C)?

AlphaMissense predicts likely pathogenic (score 0.6279) — an in-silico prediction, not a clinical call.

TRIM63 p.Gln229Pro

c.686A>C · VCV3461517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6279	likely pathogenic
REVEL	0.124	moderately benign-leaning
SaProt	LLR -14.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	24.1	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 0.00167% Admixed American · 1/60,026 alleles

Overall 6.19e-05% 1/1,614,230 alleles · very rare exomes 1/1,461,882 · genomes 0/152,348 · 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.Gln229Pro
Coding: c.686A>C
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26058535 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 229: an α-helix

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.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-gln229pro (accessed [today's date]).

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