USP7 p.Ala642=
c.1926C>T · rs140316737 · VCV2179052
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0392%, 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 -12 | GERP -4.9 |
| Overall | ||
| CADD | 0.818 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0392%
European (non-Finnish) · 462/1,179,960 alleles
Filtering AF
0.0362%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.035%
Overall
0.031%
500/1,613,836 alleles · ultra-rare
exomes 476/1,461,734 · genomes 24/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0392% | 2,554 |
| East Asian | 0.0312% | 3,205 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.00667% | 14,994 |
| South Asian | 0.0022% | 45,513 |
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.Ala642=
- Coding
- c.1926C>T
- MANE Select
- NM_003470
- dbSNP
- rs140316737
- Type
- single nucleotide variant
- Location
- chr16:8902396 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 642
- 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); a UniProt-annotated variant site (in hafous); the 'interaction with icp0/vmw110' region
Similar variants
- USP7 p.Ala642Gly Uncertain significance ★ ⚠ same residue
- 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
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-ala642 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown