Is USP20 p.Pro757Ser (c.2269C>T) pathogenic?

USP20 p.Pro757Ser (c.2269C>T) is classified Uncertain significance in USP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.5539); Absent from gnomAD v4.1.

How common is USP20 p.Pro757Ser (c.2269C>T) in the general population?

USP20 p.Pro757Ser (c.2269C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP20 p.Pro757Ser (c.2269C>T)?

AlphaMissense predicts ambiguous (score 0.5539) — an in-silico prediction, not a clinical call.

USP20 p.Pro757Ser

c.2269C>T · rs2490767286 · VCV3187259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5539 · 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	0.5539	ambiguous
REVEL	0.282	benign-leaning
SaProt	LLR -7.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 28 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	27.6	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: USP20
Protein: p.Pro757Ser
Coding: c.2269C>T
MANE Select: NM_001110303
dbSNP: rs2490767286
Type: single nucleotide variant
Location: chr9:129875610 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.11 · 1 PDB
Residue 757: the dusp 1 domain

Full USP20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP20 p.Arg330Gly Uncertain significance ★★ ⚠ same type
USP20 p.Ile907= Benign ★★ same type
USP20 p.Pro367= Benign ★★ same type
USP20 p.Ser103Tyr Benign ★★ same type
USP20 p.Ser288= Benign ★★ same type
USP20 p.Ala260Ser Uncertain significance ★ ⚠ same type
USP20 p.Ala317Thr Uncertain significance ★ ⚠ same type
USP20 p.Ala355Thr 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/usp20-p-pro757ser (accessed [today's date]).

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