USP5 p.Leu489=
c.1465C>T · rs143986399 · VCV729178
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.568%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 11.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.568%
African / African-American · 426/75,060 alleles
Filtering AF
0.523%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.505%
Overall
0.0304%
491/1,614,244 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.568% | 176 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.0464% | 2,156 |
| Admixed American | 0.035% | 2,858 |
| South Asian | 0.00878% | 11,385 |
| European (non-Finnish) | 0.000339% | 295,012 |
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
- USP5
- Protein
- p.Leu489=
- Coding
- c.1465C>T
- MANE Select
- NM_001098536
- dbSNP
- rs143986399
- Type
- single nucleotide variant
- Location
- chr12:6861073 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.40 · 12 PDB
- Residue 489
- the usp domain; a disulfide bond; a β-strand
Similar variants
- USP5 p.Leu380= Benign ★★ same type
- USP5 p.Pro609= Benign ★★ same type
- USP5 p.Val18= Benign ★★ same type
- USP5 p.Ala495Thr Uncertain significance ★ ⚠ same type
- USP5 p.Ala549Val Uncertain significance ★ ⚠ same type
- USP5 p.Ala718Thr Uncertain significance ★ ⚠ same type
- USP5 p.Ala780Ser Uncertain significance ★ ⚠ same type
- USP5 p.Arg133Trp 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/usp5-p-leu489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown