Is USP2 p.Phe573Tyr (c.1718T>A) pathogenic?

USP2 p.Phe573Tyr (c.1718T>A) is classified Uncertain significance in USP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.3039); Absent from gnomAD v4.1.

How common is USP2 p.Phe573Tyr (c.1718T>A) in the general population?

USP2 p.Phe573Tyr (c.1718T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP2 p.Phe573Tyr (c.1718T>A)?

AlphaMissense predicts likely benign (score 0.3039) — an in-silico prediction, not a clinical call.

USP2 p.Phe573Tyr

c.1718T>A · VCV4602646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3039 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,204)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3039	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.68, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00016 · regional, not allelic
Overall
CADD	23.3	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

No allele count reported in gnomAD v4.1 (AN 1,612,204). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: USP2
Protein: p.Phe573Tyr
Coding: c.1718T>A
MANE Select: NM_004205
Type: single nucleotide variant
Location: chr11:119357199 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.00 · 8 PDB
Residue 573: the usp domain; a β-strand

Full USP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP2 p.Glu93= Benign ★★ same type
USP2 p.Ala15Thr Uncertain significance ★ ⚠ same type
USP2 p.Ala244Thr Uncertain significance ★ ⚠ same type
USP2 p.Arg10His Uncertain significance ★ ⚠ same type
USP2 p.Arg148Trp Uncertain significance ★ ⚠ same type
USP2 p.Arg160Gln Uncertain significance ★ ⚠ same type
USP2 p.Arg168His Uncertain significance ★ ⚠ same type
USP2 p.Arg16Cys 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/usp2-p-phe573tyr (accessed [today's date]).

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