Is USP7 p.Ser84Thr (c.250T>A) pathogenic?

USP7 p.Ser84Thr (c.250T>A) is classified Uncertain significance in USP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1983); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with USP7 p.Ser84Thr (c.250T>A)?

USP7 p.Ser84Thr (c.250T>A) is associated with Inborn genetic diseases (ClinVar).

How common is USP7 p.Ser84Thr (c.250T>A) in the general population?

USP7 p.Ser84Thr (c.250T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP7 p.Ser84Thr (c.250T>A)?

AlphaMissense predicts likely benign (score 0.1983) — an in-silico prediction, not a clinical call.

USP7 p.Ser84Thr

c.250T>A · VCV4197930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1983	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.87	donor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser84Thr
Coding: c.250T>A
MANE Select: NM_003470
Type: single nucleotide variant
Location: chr16:8923348 (GRCh38)
Gene constraint: LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 86 PDB
Residue 84: the math domain; the 'interaction with tspyl5' region; the 'interaction with p53/tp53, mdm2 and ebna1' region; the 'necessary for nuclear localization' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USP7 p.Ser84Leu Uncertain significance ★ ⚠ same residue
USP7 p.Ser84= Likely benign ★ same residue
USP7 c.611+1G>A Likely pathogenic ★★ same condition
USP7 p.Arg919Trp Uncertain significance ★★ ⚠ same condition
USP7 p.Asp374Asn Uncertain significance ★★ ⚠ same condition
USP7 p.Glu24Val Uncertain significance ★★ ⚠ same condition
USP7 p.His3Tyr Uncertain significance ★★ ⚠ same condition
USP7 p.Ile660Val 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-ser84thr (accessed [today's date]).

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