Is USP9X p.Pro58Ser (c.172C>T) pathogenic?

USP9X p.Pro58Ser (c.172C>T) is classified Uncertain significance in USP9X (ClinVar, Single submitter, 2 submitters; last evaluated 2020-07-30). AlphaMissense: likely benign (0.0738); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 99.

What condition is associated with USP9X p.Pro58Ser (c.172C>T)?

USP9X p.Pro58Ser (c.172C>T) is associated with intellectual disability, X-linked 99 (ClinVar).

How common is USP9X p.Pro58Ser (c.172C>T) in the general population?

USP9X p.Pro58Ser (c.172C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USP9X p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

USP9X p.Pro58Ser

c.172C>T · rs1384577833 · VCV1205264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 99

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.30	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 2.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 18 kb · p 5.4e-06 · regional, not allelic
Overall
CADD	19.98	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

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: USP9X
Protein: p.Pro58Ser
Coding: c.172C>T
MANE Select: NM_001039591
dbSNP: rs1384577833
Type: single nucleotide variant
Location: chrX:41129075 (GRCh38)
Structure: AlphaFold pLDDT 80.06 · 4 PDB
Residue 58: the 'disordered' region

Full USP9X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 99 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USP9X p.Pro58Arg Uncertain significance ★ ⚠ same residue
USP9X c.323-1G>A Pathogenic/Likely pathogenic ★★ same condition
USP9X p.Arg2085His Pathogenic/Likely pathogenic ★★ same condition
USP9X p.Ala1830Gly Uncertain significance ★★ ⚠ same condition
USP9X p.Ala1948Thr Uncertain significance ★★ ⚠ same condition
USP9X p.Ala302Thr Uncertain significance ★★ ⚠ same condition
USP9X p.Ala56Gly Uncertain significance ★★ ⚠ same condition
USP9X p.Arg6Cys Uncertain significance ★★ same condition

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/usp9x-p-pro58ser (accessed [today's date]).

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