Is UMPS p.Gln430= (c.1290A>G) pathogenic?

UMPS p.Gln430= (c.1290A>G) is classified Conflicting classifications of pathogenicity in UMPS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-08). Low-frequency (popmax 2.03%, sas); Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Gln430= (c.1290A>G)?

UMPS p.Gln430= (c.1290A>G) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Gln430= (c.1290A>G) in the general population?

UMPS p.Gln430= (c.1290A>G) is low-frequency (popmax 2.03%, sas) (gnomAD).

UMPS p.Gln430=

c.1290A>G · rs17843847 · VCV790937

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, sas)

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 -1.5	GERP -5.4
Overall
CADD	1.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.03% South Asian · 1,846/91,080 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.92%

Overall 0.123% 1,981/1,614,196 alleles · low-frequency exomes 1,856/1,461,820 · genomes 125/152,376 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.03%	49
Remaining individualsnot grpmax-eligible	0.142%	702
Middle Eastern	0.132%	758
European (non-Finnish)	0.00305%	32,778
Admixed American	0.00167%	60,028
African / African-American	0.00133%	75,076

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: UMPS
Protein: p.Gln430=
Coding: c.1290A>G
MANE Select: NM_000373
dbSNP: rs17843847
Type: single nucleotide variant
Location: chr3:124743931 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 430: a binding site; the 'ompdecase' region

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-gln430 (accessed [today's date]).

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