Is USP47 p.Pro596Arg (c.1787C>G) pathogenic?

USP47 p.Pro596Arg (c.1787C>G) is classified Uncertain significance in USP47 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely pathogenic (0.8504); Absent from gnomAD v4.1.

How common is USP47 p.Pro596Arg (c.1787C>G) in the general population?

USP47 p.Pro596Arg (c.1787C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP47 p.Pro596Arg (c.1787C>G)?

AlphaMissense predicts likely pathogenic (score 0.8504) — an in-silico prediction, not a clinical call.

USP47 p.Pro596Arg

c.1787C>G · rs369697716 · VCV3187699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8504 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8504	likely pathogenic
REVEL	0.452	indeterminate
SaProt	LLR -13.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 33 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P616R vs ClinVar P596R) — verify the residue.

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: USP47
Protein: p.Pro596Arg
Coding: c.1787C>G
MANE Select: NM_001282659
dbSNP: rs369697716
Type: single nucleotide variant
Location: chr11:11933853 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.63

Full USP47 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP47 c.970-2A>G Uncertain significance ★ same type
USP47 p.Ala1124Val Uncertain significance ★ ⚠ same type
USP47 p.Ala1293Val Uncertain significance ★ ⚠ same type
USP47 p.Ala419Thr Uncertain significance ★ same type
USP47 p.Ala617Val Uncertain significance ★ ⚠ same type
USP47 p.Ala709Ser Uncertain significance ★ ⚠ same type
USP47 p.Ala95Thr Uncertain significance ★ ⚠ same type
USP47 p.Arg1076Trp 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/usp47-p-pro596arg (accessed [today's date]).

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