Is USP1 p.Ser287Pro (c.859T>C) pathogenic?

USP1 p.Ser287Pro (c.859T>C) is classified Uncertain significance in USP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0674); Ultra-rare (popmax 0.0198%, sas).

How common is USP1 p.Ser287Pro (c.859T>C) in the general population?

USP1 p.Ser287Pro (c.859T>C) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

What do computational predictors say about USP1 p.Ser287Pro (c.859T>C)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

USP1 p.Ser287Pro

c.859T>C · rs776525311 · VCV2232651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -8.14	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 1.2	GERP 0.29, phastCons 0.015
Regional constraint	o/e 1.02	unconstrained · MANE · 2,548 bp · p 0.78 · regional, not allelic
Overall
CADD	15.21	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

Grpmax group 0.0198% South Asian · 18/90,924 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00118% 19/1,613,020 alleles · ultra-rare exomes 19/1,460,914 · genomes 0/152,106 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,051
African / African-American	0.00134%	74,838

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: USP1
Protein: p.Ser287Pro
Coding: c.859T>C
MANE Select: NM_003368
dbSNP: rs776525311
Type: single nucleotide variant
Location: chr1:62445039 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.24 · 15 PDB
Residue 287: the usp domain; the 'disordered' region

Full USP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP1 p.Ala632Val Uncertain significance ★ ⚠ same type
USP1 p.Ala64Val Uncertain significance ★ ⚠ same type
USP1 p.Ala694Val Uncertain significance ★ ⚠ same type
USP1 p.Arg329Gly Uncertain significance ★ ⚠ same type
USP1 p.Arg439His Uncertain significance ★ same type
USP1 p.Arg633Gly Uncertain significance ★ ⚠ same type
USP1 p.Asn364Lys Uncertain significance ★ ⚠ same type
USP1 p.Asn682Ser 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/usp1-p-ser287pro (accessed [today's date]).

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