Is USP30 p.Pro389Ser (c.1165C>T) pathogenic?

USP30 p.Pro389Ser (c.1165C>T) is classified Likely benign in USP30 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0621); Ultra-rare (popmax 0.0134%, eas).

How common is USP30 p.Pro389Ser (c.1165C>T) in the general population?

USP30 p.Pro389Ser (c.1165C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about USP30 p.Pro389Ser (c.1165C>T)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

USP30 p.Pro389Ser

c.1165C>T · rs147931793 · VCV3187374

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.24	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 -1.4	GERP -0.59
Regional constraint	o/e 0.80	unconstrained · MANE · 33 kb · p 5.8e-07 · regional, not allelic
Overall
CADD	0.215	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

Grpmax group 0.0134% East Asian · 6/44,794 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000936% 15/1,602,972 alleles · ultra-rare exomes 11/1,450,740 · genomes 4/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,466
European (non-Finnish)	0.000766%	130,522

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: USP30
Protein: p.Pro389Ser
Coding: c.1165C>T
MANE Select: NM_032663
dbSNP: rs147931793
Type: single nucleotide variant
Location: chr12:109083059 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.29 · 8 PDB
Residue 389: the usp domain; the 'disordered' region

Full USP30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP30 p.Ala12Val Uncertain significance ★ ⚠ same type
USP30 p.Ala25Glu Uncertain significance ★ ⚠ same type
USP30 p.Ala25Thr Uncertain significance ★ ⚠ same type
USP30 p.Ala396Asp Uncertain significance ★ ⚠ same type
USP30 p.Ala417Val Uncertain significance ★ ⚠ same type
USP30 p.Ala494Thr Uncertain significance ★ ⚠ same type
USP30 p.Ala6Thr Uncertain significance ★ ⚠ same type
USP30 p.Arg105Gly 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/usp30-p-pro389ser (accessed [today's date]).

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