Is TRIM63 p.Arg62Gln (c.185G>A) pathogenic?

TRIM63 p.Arg62Gln (c.185G>A) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1993); Very rare (popmax 0.00447%, eas); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Arg62Gln (c.185G>A)?

TRIM63 p.Arg62Gln (c.185G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Arg62Gln (c.185G>A) in the general population?

TRIM63 p.Arg62Gln (c.185G>A) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about TRIM63 p.Arg62Gln (c.185G>A)?

AlphaMissense predicts likely benign (score 0.1993) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg62Gln

c.185G>A · rs369627227 · VCV2220588

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1993	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	27.9	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 0.00447% East Asian · 2/44,716 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00287% 46/1,603,608 alleles · very rare exomes 42/1,451,284 · genomes 4/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,358
African / African-American	0.004%	24,973
Ashkenazi Jewishnot grpmax-eligible	0.00346%	28,924
European (non-Finnish)	0.00332%	30,104
Remaining individualsnot grpmax-eligible	0.00161%	62,084

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.Arg62Gln
Coding: c.185G>A
MANE Select: NM_032588
dbSNP: rs369627227
Type: single nucleotide variant
Location: chr1:26066415 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB

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.Arg62Trp Uncertain significance ★★ ⚠ 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.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-arg62gln (accessed [today's date]).

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