Is TRIM63 p.Pro57Arg (c.170C>G) pathogenic?

TRIM63 p.Pro57Arg (c.170C>G) is classified Uncertain significance in TRIM63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-24). AlphaMissense: ambiguous (0.5504); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Pro57Arg (c.170C>G)?

TRIM63 p.Pro57Arg (c.170C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Pro57Arg (c.170C>G) in the general population?

TRIM63 p.Pro57Arg (c.170C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRIM63 p.Pro57Arg (c.170C>G)?

AlphaMissense predicts ambiguous (score 0.5504) — an in-silico prediction, not a clinical call.

TRIM63 p.Pro57Arg

c.170C>G · rs146641597 · VCV2581237

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5504 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5504	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -15.36	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	29.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRIM63
Protein: p.Pro57Arg
Coding: c.170C>G
MANE Select: NM_032588
dbSNP: rs146641597
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.Pro57Leu 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-pro57arg (accessed [today's date]).

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