USP7 p.Ser149=
c.447G>A · VCV4753073
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, 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 -7.3 | GERP -4.6 |
| Overall | ||
| CADD | 2.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,926 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.00211%
34/1,613,940 alleles · ultra-rare
exomes 23/1,461,760 · genomes 11/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,683 |
| Finnishnot grpmax-eligible | 0.00625% | 15,990 |
| Admixed American | 0.005% | 20,002 |
| South Asian | 0.00439% | 22,772 |
| European (non-Finnish) | 0.000593% | 168,572 |
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.Ser149=
- Coding
- c.447G>A
- MANE Select
- NM_003470
- Type
- single nucleotide variant
- Location
- chr16:8921232 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 149
- the math 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); the 'interaction with tspyl5' region; the 'interaction with p53/tp53, mdm2 and ebna1' region; the 'necessary for nuclear localization' region
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-ser149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown