TRIM63 p.Glu269=
c.807G>A · rs1173414010 · VCV3895050
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 2.1 | GERP -0.05, phastCons 1 |
| Overall | ||
| CADD | 9.381 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,932 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00112%
18/1,614,044 alleles · very rare
exomes 14/1,461,858 · genomes 4/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,466 |
| European (non-Finnish) | 0.00136% | 73,753 |
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.Glu269=
- Coding
- c.807G>A
- MANE Select
- NM_032588
- dbSNP
- rs1173414010
- Type
- single nucleotide variant
- Location
- chr1:26058414 (GRCh38)
- Gene constraint
- LOEUF 1.329 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.88 · 3 PDB
- Residue 269
- the cos domain; a UniProt-annotated variant site (in cmh31; likely pathogenic; no protein detected in patient cells; loss of function in protein ubiquitination)
Similar variants
- TRIM63 p.Glu269Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-glu269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown