Is USP10 p.Pro548Ala (c.1642C>G) pathogenic?

USP10 p.Pro548Ala (c.1642C>G) is classified Uncertain significance in USP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.0721); Ultra-rare (popmax 0.0333%, afr).

How common is USP10 p.Pro548Ala (c.1642C>G) in the general population?

USP10 p.Pro548Ala (c.1642C>G) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

What do computational predictors say about USP10 p.Pro548Ala (c.1642C>G)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

USP10 p.Pro548Ala

c.1642C>G · VCV3814002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -9.59	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 2.2	GERP 0.92, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 64 kb · p 0.0033 · regional, not allelic
Overall
CADD	21.1	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 0.0333% African / African-American · 25/74,984 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00186% 30/1,609,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	2,999
Admixed American	0.00835%	11,975

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: USP10
Protein: p.Pro548Ala
Coding: c.1642C>G
MANE Select: NM_005153
Type: single nucleotide variant
Location: chr16:84763076 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.19 · 2 PDB
Residue 548: the usp domain

Full USP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP10 p.Ala108Gly Uncertain significance ★ ⚠ same type
USP10 p.Ala123Thr Uncertain significance ★ ⚠ same type
USP10 p.Ala132Ser Uncertain significance ★ ⚠ same type
USP10 p.Ala239Ser Uncertain significance ★ ⚠ same type
USP10 p.Ala259Gly Uncertain significance ★ ⚠ same type
USP10 p.Ala270Thr Uncertain significance ★ ⚠ same type
USP10 p.Ala298Pro Uncertain significance ★ ⚠ same type
USP10 p.Ala320Val 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/usp10-p-pro548ala (accessed [today's date]).

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