Is TRIM63 p.Arg86Cys (c.256C>T) pathogenic?

TRIM63 p.Arg86Cys (c.256C>T) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). AlphaMissense: likely pathogenic (0.8789); Very rare (popmax 0.00329%, sas).

How common is TRIM63 p.Arg86Cys (c.256C>T) in the general population?

TRIM63 p.Arg86Cys (c.256C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about TRIM63 p.Arg86Cys (c.256C>T)?

AlphaMissense predicts likely pathogenic (score 0.8789) — an in-silico prediction, not a clinical call.

TRIM63 p.Arg86Cys

c.256C>T · VCV3893684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8789	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -11.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP -1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	34.0	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 0.00329% South Asian · 3/91,062 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00124% 20/1,614,010 alleles · very rare exomes 19/1,461,714 · genomes 1/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,354
Admixed American	0.00167%	60,022
African / African-American	0.00133%	75,052
European (non-Finnish)	0.00127%	78,661

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.Arg86Cys
Coding: c.256C>T
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26066344 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 86: a UniProt-annotated variant site (in cmh31; uncertain significance); the 'interaction with ttn' region

Full TRIM63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM63 p.Ala244Val Uncertain significance ★★ ⚠ same type
TRIM63 p.Ala289Val Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg112Gln Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg183His Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg230Trp Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg62Gln Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg62Trp Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg74His Uncertain significance ★★ ⚠ same type

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-arg86cys (accessed [today's date]).

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