Is TRIM63 p.Pro57Leu (c.170C>T) pathogenic?

TRIM63 p.Pro57Leu (c.170C>T) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: ambiguous (0.4452); Ultra-rare (popmax 0.0593%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Pro57Leu (c.170C>T)?

TRIM63 p.Pro57Leu (c.170C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Pro57Leu (c.170C>T) in the general population?

TRIM63 p.Pro57Leu (c.170C>T) is ultra-rare (popmax 0.0593%, afr) (gnomAD).

What do computational predictors say about TRIM63 p.Pro57Leu (c.170C>T)?

AlphaMissense predicts ambiguous (score 0.4452) — an in-silico prediction, not a clinical call.

TRIM63 p.Pro57Leu

c.170C>T · VCV3810596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4452 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0593%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4452	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -13.71	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	29.0	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 0.0593% African / African-American · 44/74,216 alleles

Filtering AF 0.0453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0404%

Overall 0.00322% 51/1,582,192 alleles · ultra-rare exomes 24/1,429,972 · genomes 27/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0593%	1,687
Admixed American	0.00175%	57,220
Remaining individualsnot grpmax-eligible	0.00164%	61,062
European (non-Finnish)	0.00043%	232,347

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.Pro57Leu
Coding: c.170C>T
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26066430 (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.Pro57Arg 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.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

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-pro57leu (accessed [today's date]).

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