Is USP10 p.Ala239Ser (c.715G>T) pathogenic?

USP10 p.Ala239Ser (c.715G>T) is classified Uncertain significance in USP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0923); Very rare (popmax 0.00916%, nfe).

How common is USP10 p.Ala239Ser (c.715G>T) in the general population?

USP10 p.Ala239Ser (c.715G>T) is very rare (popmax 0.00916%, nfe) (gnomAD).

What do computational predictors say about USP10 p.Ala239Ser (c.715G>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

USP10 p.Ala239Ser

c.715G>T · VCV4602532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00916%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -5.76	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 9.9	GERP 0.97, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 64 kb · p 0.0033 · regional, not allelic
Overall
CADD	22.0	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 0.00916% European (non-Finnish) · 108/1,179,628 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.00688% 111/1,613,236 alleles · very rare exomes 110/1,460,994 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00916%	10,922
Remaining individualsnot grpmax-eligible	0.0048%	20,812

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.Ala239Ser
Coding: c.715G>T
MANE Select: NM_005153
Type: single nucleotide variant
Location: chr16:84745196 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.19 · 2 PDB
Residue 239: the 'disordered' region

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.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
USP10 p.Ala358Pro 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-ala239ser (accessed [today's date]).

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