Is USP3 p.Pro14Gln (c.41C>A) pathogenic?

USP3 p.Pro14Gln (c.41C>A) is classified Uncertain significance in USP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely benign (0.1438); No allele count reported in gnomAD v4.1 (AN 1,611,446).

How common is USP3 p.Pro14Gln (c.41C>A) in the general population?

USP3 p.Pro14Gln (c.41C>A) is no allele count reported in gnomAD v4.1 (AN 1,611,446) (gnomAD).

What do computational predictors say about USP3 p.Pro14Gln (c.41C>A)?

AlphaMissense predicts likely benign (score 0.1438) — an in-silico prediction, not a clinical call.

USP3 p.Pro14Gln

c.41C>A · rs2550681653 · VCV2290050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1438 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,446)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1438	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 86 kb · p 7.7e-10 · regional, not allelic
Overall
CADD	21.7	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

No allele count reported in gnomAD v4.1 (AN 1,611,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: USP3
Protein: p.Pro14Gln
Coding: c.41C>A
MANE Select: NM_006537
dbSNP: rs2550681653
Type: single nucleotide variant
Location: chr15:63504780 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.40

Full USP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP3 p.Pro360Thr Benign ★★ same type
USP3 p.Ala306Glu Uncertain significance ★ ⚠ same type
USP3 p.Ala64Thr Uncertain significance ★ ⚠ same type
USP3 p.Arg204Gln Uncertain significance ★ same type
USP3 p.Arg204Trp Uncertain significance ★ ⚠ same type
USP3 p.Arg332Thr Uncertain significance ★ ⚠ same type
USP3 p.Arg33Leu Uncertain significance ★ ⚠ same type
USP3 p.Arg352Cys 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/usp3-p-pro14gln (accessed [today's date]).

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