Is USP7 p.Val1020= (c.3060G>C) pathogenic?

USP7 p.Val1020= (c.3060G>C) is classified Benign in USP7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Low-frequency (popmax 3.5%, nfe).

How common is USP7 p.Val1020= (c.3060G>C) in the general population?

USP7 p.Val1020= (c.3060G>C) is low-frequency (popmax 3.5%, nfe) (gnomAD).

USP7 p.Val1020=

c.3060G>C · rs11551183 · VCV2037480

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.5%, 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 -0.48	GERP -4.1, phastCons 0.017
Overall
CADD	2.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.5% European (non-Finnish) · 41,313/1,180,048 alleles

Filtering AF 3.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 3.02% 48,764/1,614,206 alleles · low-frequency exomes 45,459/1,461,886 · genomes 3,305/152,320 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	7.35%	14
Amishnot grpmax-eligible	6.17%	16
European (non-Finnish)grpmax	3.5%	29
Remaining individualsnot grpmax-eligible	3.01%	33
Finnishnot grpmax-eligible	2.23%	45
South Asian	1.01%	99
Admixed American	0.793%	126
African / African-American	0.639%	156
Middle Eastern	0.528%	189

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1020=
Coding: c.3060G>C
MANE Select: NM_003470
dbSNP: rs11551183
Type: single nucleotide variant
Location: chr16:8894835 (GRCh38)
Gene constraint: LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 86 PDB
Residue 1020: 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)

Full USP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP7 p.Val1020Leu 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-val1020 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown