USP7 p.Leu469=
c.1407A>G · rs144447086 · VCV726816
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.5%, 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 -6.2 | GERP -5.2 |
| Overall | ||
| CADD | 0.373 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.5%
African / African-American · 1,126/74,984 alleles
Filtering AF
1.43%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4%
Overall
0.0795%
1,281/1,612,196 alleles · low-frequency
exomes 636/1,459,848 · genomes 645/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.5% | 67 |
| Admixed American | 0.122% | 822 |
| Remaining individualsnot grpmax-eligible | 0.104% | 959 |
| South Asian | 0.00769% | 12,997 |
| European (non-Finnish) | 0.000847% | 117,998 |
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
- USP7
- Protein
- p.Leu469=
- Coding
- c.1407A>G
- MANE Select
- NM_003470
- dbSNP
- rs144447086
- Type
- single nucleotide variant
- Location
- chr16:8906447 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 469
- the usp domain; a UniProt-annotated variant site (in hafous; when expressed in usp7-deficient cells does not rescue defective endosomal protein recycling and reduced f-actin levels); a β-strand
Similar variants
- USP7 c.611+1G>A Likely pathogenic ★★ same type
- USP7 p.Arg1018Ter Pathogenic/Likely pathogenic ★★ same type
- USP7 p.Arg239Ter Pathogenic ★★ same type
- USP7 p.Arg508Ter Pathogenic ★★ same type
- USP7 p.Gln866Ter Pathogenic/Likely pathogenic ★★ same type
- USP7 c.3039+3A>G Uncertain significance ★★ same type
- USP7 c.852-4A>G Uncertain significance ★★ same type
- USP7 p.Ala27= 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/usp7-p-leu469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown