Is USP7 p.Arg892Ter (c.2674C>T) pathogenic?

USP7 p.Arg892Ter (c.2674C>T) is classified Likely pathogenic in USP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). Absent from gnomAD v4.1; Associated with USP7-related disorder.

What condition is associated with USP7 p.Arg892Ter (c.2674C>T)?

USP7 p.Arg892Ter (c.2674C>T) is associated with USP7-related disorder (ClinVar).

How common is USP7 p.Arg892Ter (c.2674C>T) in the general population?

USP7 p.Arg892Ter (c.2674C>T) is absent from gnomAD v4.1 (gnomAD).

USP7 p.Arg892Ter

c.2674C>T · VCV4928477

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

USP7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 25 of 31
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Pangolin	Δ0.22	loss · gain 0.10 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 2.4	GERP 0.022, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: USP7
Protein: p.Arg892Ter
Coding: c.2674C>T
MANE Select: NM_003470
Type: single nucleotide variant
Location: chr16:8898404 (GRCh38)
Gene constraint: LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 86 PDB
Residue 892: 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

Disease context

USP7-related disorder

Similar variants

USP7 p.Arg892= Likely benign ★ same residue
USP7 p.Gln1031Glu Uncertain significance ★★ ⚠ same condition
USP7 p.Arg301Gly Likely pathogenic ★ same condition
USP7 p.Lys984Ter Likely pathogenic ★ same condition
USP7 p.Ala642Gly Uncertain significance ★ ⚠ same condition
USP7 p.Asn53Ser Uncertain significance ★ ⚠ same condition
USP7 p.Gly28Arg Uncertain significance ★ ⚠ same condition
USP7 c.80-6195G>A Uncertain significance same condition

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-arg892ter (accessed [today's date]).

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