Is UMPS p.Val350= (c.1050T>A) pathogenic?

UMPS p.Val350= (c.1050T>A) is classified Benign in UMPS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Val350= (c.1050T>A)?

UMPS p.Val350= (c.1050T>A) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

UMPS p.Val350=

Q: How common is UMPS p.Val350= (c.1050T>A) in the general population?

UMPS p.Val350= (c.1050T>A) is common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1050T>A · rs2291078 · VCV100129

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele

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 -4.7	GERP -5.5
Overall
CADD	1.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.63% East Asian · 3,424/44,886 alleles

Filtering AF 7.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.33%

Overall 1.66% 26,862/1,614,088 alleles · common exomes 24,727/1,461,876 · genomes 2,135/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	7.63%	13
South Asian	5.18%	19
Admixed American	3.89%	26
Remaining individualsnot grpmax-eligible	1.7%	59
European (non-Finnish)	1.22%	82
Ashkenazi Jewishnot grpmax-eligible	0.841%	119
Finnishnot grpmax-eligible	0.698%	143
Middle Eastern	0.528%	189
African / African-American	0.296%	338

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.Val350=
Coding: c.1050T>A
MANE Select: NM_000373
dbSNP: rs2291078
Type: single nucleotide variant
Location: chr3:124740091 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 350: 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.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-val350 (accessed [today's date]).

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