Is UMPS p.Ser241= (c.723G>A) pathogenic?

UMPS p.Ser241= (c.723G>A) is classified Likely benign in UMPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-18). Ultra-rare (popmax 0.0134%, eas); Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Ser241= (c.723G>A)?

UMPS p.Ser241= (c.723G>A) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Ser241= (c.723G>A) in the general population?

UMPS p.Ser241= (c.723G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

UMPS p.Ser241=

c.723G>A · VCV3671965

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -5.8	GERP -5.2
Overall
CADD	0.879	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,902 alleles

Filtering AF 0.00578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00118% 19/1,614,040 alleles · ultra-rare exomes 17/1,461,860 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,484
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000763%	131,114

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.Ser241=
Coding: c.723G>A
MANE Select: NM_000373
Type: single nucleotide variant
Location: chr3:124737980 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 241: the 'ompdecase' 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.Ser241Leu Uncertain significance ★ ⚠ same residue
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

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-ser241 (accessed [today's date]).

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