Is TRIM63 p.Arg183Cys (c.547C>T) pathogenic?

TRIM63 p.Arg183Cys (c.547C>T) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.2997); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Arg183Cys (c.547C>T)?

TRIM63 p.Arg183Cys (c.547C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Arg183Cys (c.547C>T) in the general population?

TRIM63 p.Arg183Cys (c.547C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about TRIM63 p.Arg183Cys (c.547C>T)?

AlphaMissense predicts likely benign (score 0.2997) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg183Cys

c.547C>T · VCV3810600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2997	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	26.1	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 0.00534% African / African-American · 4/74,892 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00118% 19/1,613,892 alleles · very rare exomes 14/1,461,766 · genomes 5/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,723
East Asian	0.00446%	22,446
European (non-Finnish)	0.0011%	90,769

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.Arg183Cys
Coding: c.547C>T
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26060316 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 183: 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.Arg183His Uncertain significance ★★ ⚠ same residue
TRIM63 p.Arg112Gln 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-arg183cys (accessed [today's date]).

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