Is TRIM63 p.Arg230Trp (c.688C>T) pathogenic?

TRIM63 p.Arg230Trp (c.688C>T) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-26). AlphaMissense: likely benign (0.1462); Ultra-rare (popmax 0.0307%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Arg230Trp (c.688C>T)?

TRIM63 p.Arg230Trp (c.688C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Arg230Trp (c.688C>T) in the general population?

TRIM63 p.Arg230Trp (c.688C>T) is ultra-rare (popmax 0.0307%, nfe) (gnomAD).

What do computational predictors say about TRIM63 p.Arg230Trp (c.688C>T)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg230Trp

c.688C>T · rs368646276 · VCV2247024

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -10.35	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 3.1	GERP -1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	25.7	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 0.0307% European (non-Finnish) · 362/1,180,042 alleles

Filtering AF 0.0281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.027%

Overall 0.0244% 394/1,614,060 alleles · ultra-rare exomes 373/1,461,886 · genomes 21/152,174 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)grpmax	0.0307%	3,260
Middle Eastern	0.0164%	6,084
African / African-American	0.00534%	18,728
South Asian	0.00329%	30,363

Remaining individuals 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.Arg230Trp
Coding: c.688C>T
MANE Select: NM_032588
dbSNP: rs368646276
Type: single nucleotide variant
Location: chr1:26058533 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 230: 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.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
TRIM63 p.Tyr105Cys 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-arg230trp (accessed [today's date]).

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