Is TRIM63 p.Pro140= (c.420C>A) pathogenic?

TRIM63 p.Pro140= (c.420C>A) is classified Likely benign in TRIM63 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-12-24). Absent from gnomAD v4.1; Associated with TRIM63-related disorder.

What condition is associated with TRIM63 p.Pro140= (c.420C>A)?

TRIM63 p.Pro140= (c.420C>A) is associated with TRIM63-related disorder (ClinVar).

How common is TRIM63 p.Pro140= (c.420C>A) in the general population?

TRIM63 p.Pro140= (c.420C>A) is absent from gnomAD v4.1 (gnomAD).

TRIM63 p.Pro140=

c.420C>A · rs2522760749 · VCV3030012

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

TRIM63-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 2.3, phastCons 1
Overall
CADD	8.978	PHRED · no single calibrated threshold — expert panels disagree

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.Pro140=
Coding: c.420C>A
MANE Select: NM_032588
dbSNP: rs2522760749
Type: single nucleotide variant
Location: chr1:26061247 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 140: the 'interaction with ttn' region; a β-strand

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

Disease context

TRIM63-related disorder

Similar variants

TRIM63 c.831+2T>G Uncertain significance ★ same condition
TRIM63 p.Glu208= Likely benign same condition
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

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-pro140 (accessed [today's date]).

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