USP7 p.Asp535=
c.1605T>C · rs762840813 · VCV1970820
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, nfe)
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 0.72 | GERP -4.5, phastCons 0.98 |
| Overall | ||
| CADD | 7.367 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,180,048 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00097%
Overall
0.0013%
21/1,614,058 alleles · very rare
exomes 20/1,461,852 · genomes 1/152,206 · joint denominator
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.Asp535=
- Coding
- c.1605T>C
- MANE Select
- NM_003470
- dbSNP
- rs762840813
- Type
- single nucleotide variant
- Location
- chr16:8904534 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 535
- an α-helix; 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)
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-asp535 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown