USP7 p.Thr247=
c.741C>T · rs778073082 · VCV1914261
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 -2.3 | GERP -4.6 |
| Overall | ||
| CADD | 6.881 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,852 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00304%
49/1,612,336 alleles · ultra-rare
exomes 45/1,460,372 · genomes 4/151,964 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,970 |
| European (non-Finnish) | 0.00356% | 28,087 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,444 |
| African / African-American | 0.00134% | 74,774 |
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.Thr247=
- Coding
- c.741C>T
- MANE Select
- NM_003470
- dbSNP
- rs778073082
- Type
- single nucleotide variant
- Location
- chr16:8917136 (GRCh38)
- Gene constraint
- LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.50 · 86 PDB
- Residue 247
- 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)
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-thr247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown