Is TRIM63 p.Arg183His (c.548G>A) pathogenic?

TRIM63 p.Arg183His (c.548G>A) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1515); Ultra-rare (popmax 0.024%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Arg183His (c.548G>A)?

TRIM63 p.Arg183His (c.548G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Arg183His (c.548G>A) in the general population?

TRIM63 p.Arg183His (c.548G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about TRIM63 p.Arg183His (c.548G>A)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg183His

c.548G>A · rs139003247 · VCV2544614

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,032 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00458% 74/1,614,066 alleles · ultra-rare exomes 62/1,461,782 · genomes 12/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,168
Remaining individualsnot grpmax-eligible	0.0096%	10,418
East Asian	0.00668%	14,961
Finnishnot grpmax-eligible	0.00469%	21,321
Admixed American	0.00333%	30,004
European (non-Finnish)	0.00331%	30,257
South Asian	0.00329%	30,360

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.Arg183His
Coding: c.548G>A
MANE Select: NM_032588
dbSNP: rs139003247
Type: single nucleotide variant
Location: chr1:26060315 (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.Arg183Cys 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-arg183his (accessed [today's date]).

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