USP7 p.Ser601=
c.1803G>A · VCV3706507
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0527%, sas)
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 -8.5 | GERP -4.8 |
| Overall | ||
| CADD | 0.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0527%
South Asian · 48/91,042 alleles
Filtering AF
0.0408%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.00533%
86/1,613,806 alleles · ultra-rare
exomes 79/1,461,646 · genomes 7/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0527% | 1,897 |
| Middle Eastern | 0.0165% | 6,070 |
| African / African-American | 0.012% | 8,322 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| Admixed American | 0.00333% | 29,991 |
| European (non-Finnish) | 0.00195% | 51,301 |
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.Ser601=
- Coding
- c.1803G>A
- MANE Select
- NM_003470
- Type
- single nucleotide variant
- Location
- chr16:8903304 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 601
- 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)
Similar variants
- USP7 p.Ser601Leu Benign ★ 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-ser601 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown