Is UMPS p.Leu15= (c.45G>A) pathogenic?

UMPS p.Leu15= (c.45G>A) is classified Likely benign in UMPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Leu15= (c.45G>A)?

UMPS p.Leu15= (c.45G>A) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Leu15= (c.45G>A) in the general population?

UMPS p.Leu15= (c.45G>A) is absent from gnomAD v4.1 (gnomAD).

UMPS p.Leu15=

c.45G>A · rs769561118 · VCV2058578

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hereditary orotic aciduria, type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 0.59, phastCons 1
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

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: UMPS
Protein: p.Leu15=
Coding: c.45G>A
MANE Select: NM_000373
dbSNP: rs769561118
Type: single nucleotide variant
Location: chr3:124730516 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 15: the 'oprtase' region; an α-helix

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

Disease context

Hereditary orotic aciduria, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UMPS p.Ala4Pro Uncertain significance ★★ ⚠ same condition
UMPS p.Arg313Trp Uncertain significance ★★ ⚠ same condition
UMPS p.Gly167Arg Uncertain significance ★★ ⚠ same condition
UMPS p.Ser276Asn Uncertain significance ★★ ⚠ same condition
UMPS p.Ser404Phe Uncertain significance ★★ ⚠ same condition
UMPS c.1159-19C>T Likely benign ★★ same condition
UMPS c.*28A>G Benign ★★ same condition
UMPS p.Gly213Ala Benign ★★ 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/umps-p-leu15 (accessed [today's date]).

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