Is USP7 p.Val203Ile (c.607G>A) pathogenic?

USP7 p.Val203Ile (c.607G>A) is classified Uncertain significance in USP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.3319); Absent from gnomAD v4.1.

How common is USP7 p.Val203Ile (c.607G>A) in the general population?

USP7 p.Val203Ile (c.607G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP7 p.Val203Ile (c.607G>A)?

AlphaMissense predicts likely benign (score 0.3319) — an in-silico prediction, not a clinical call.

USP7 p.Val203Ile

c.607G>A · VCV4529881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3319 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3319	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 4,910 bp · p 1.6e-25 · regional, not allelic
Overall
CADD	23.7	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.Val203Ile
Coding: c.607G>A
MANE Select: NM_003470
Type: single nucleotide variant
Location: chr16:8920363 (GRCh38)
Gene constraint: LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 86 PDB
Residue 203: 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; a β-strand

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

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-val203ile (accessed [today's date]).

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