Is UMPS p.Ser444= (c.1332C>T) pathogenic?

UMPS p.Ser444= (c.1332C>T) is classified Likely benign in UMPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-13). Ultra-rare (popmax 0.0156%, eas); Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Ser444= (c.1332C>T)?

UMPS p.Ser444= (c.1332C>T) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Ser444= (c.1332C>T) in the general population?

UMPS p.Ser444= (c.1332C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

UMPS p.Ser444=

c.1332C>T · rs112541424 · VCV2738881

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, 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 -0.2	GERP -0.91, phastCons 0.68
Overall
CADD	13.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,892 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.0039% 63/1,614,014 alleles · ultra-rare exomes 56/1,461,866 · genomes 7/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.0107%	9,363
Admixed American	0.00833%	11,999
South Asian	0.00439%	22,771
European (non-Finnish)	0.00254%	39,335

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.Ser444=
Coding: c.1332C>T
MANE Select: NM_000373
dbSNP: rs112541424
Type: single nucleotide variant
Location: chr3:124743973 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 444: 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-ser444 (accessed [today's date]).

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