Is TRIM63 p.Ala179Val (c.536C>T) pathogenic?

TRIM63 p.Ala179Val (c.536C>T) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-10). AlphaMissense: ambiguous (0.4985); Very rare (popmax 0.00668%, eas).

How common is TRIM63 p.Ala179Val (c.536C>T) in the general population?

TRIM63 p.Ala179Val (c.536C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about TRIM63 p.Ala179Val (c.536C>T)?

AlphaMissense predicts ambiguous (score 0.4985) — an in-silico prediction, not a clinical call.

TRIM63 p.Ala179Val

c.536C>T · VCV4848679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4985	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -9.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 1.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	32.0	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 0.00668% East Asian · 3/44,890 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00347% 56/1,613,788 alleles · very rare exomes 47/1,461,692 · genomes 9/152,096 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
African / African-American	0.00401%	24,959
European (non-Finnish)	0.00398%	25,105
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,476
South Asian	0.0011%	91,076

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.Ala179Val
Coding: c.536C>T
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26060327 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 179: 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-ala179val (accessed [today's date]).

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