Is TRIM63 p.Asp50Tyr (c.148G>T) pathogenic?

TRIM63 p.Asp50Tyr (c.148G>T) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.8965); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRIM63 p.Asp50Tyr (c.148G>T)?

TRIM63 p.Asp50Tyr (c.148G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIM63 p.Asp50Tyr (c.148G>T) in the general population?

TRIM63 p.Asp50Tyr (c.148G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRIM63 p.Asp50Tyr (c.148G>T)?

AlphaMissense predicts likely pathogenic (score 0.8965) — an in-silico prediction, not a clinical call.

TRIM63 p.Asp50Tyr

c.148G>T · rs2522777887 · VCV2474892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8965	likely pathogenic
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -16.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.51 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp50Tyr
Coding: c.148G>T
MANE Select: NM_032588
dbSNP: rs2522777887
Type: single nucleotide variant
Location: chr1:26067347 (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.Asp50Gly 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-asp50tyr (accessed [today's date]).

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