Is USP2 p.Met554Ile (c.1662G>C) pathogenic?

USP2 p.Met554Ile (c.1662G>C) is classified Uncertain significance in USP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: ambiguous (0.5624); Absent from gnomAD v4.1.

How common is USP2 p.Met554Ile (c.1662G>C) in the general population?

USP2 p.Met554Ile (c.1662G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP2 p.Met554Ile (c.1662G>C)?

AlphaMissense predicts ambiguous (score 0.5624) — an in-silico prediction, not a clinical call.

USP2 p.Met554Ile

c.1662G>C · rs1950680357 · VCV3187238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5624 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5624	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -8.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.63, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00016 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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: USP2
Protein: p.Met554Ile
Coding: c.1662G>C
MANE Select: NM_004205
dbSNP: rs1950680357
Type: single nucleotide variant
Location: chr11:119357255 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.00 · 8 PDB
Residue 554: 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-met554ile (accessed [today's date]).

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