Is UMPS p.Ala7= (c.21T>C) pathogenic?

UMPS p.Ala7= (c.21T>C) is classified Benign/Likely benign in UMPS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.21%, afr); Associated with Oroticaciduria.

What condition is associated with UMPS p.Ala7= (c.21T>C)?

UMPS p.Ala7= (c.21T>C) is associated with Oroticaciduria (ClinVar).

How common is UMPS p.Ala7= (c.21T>C) in the general population?

UMPS p.Ala7= (c.21T>C) is low-frequency (popmax 1.21%, afr) (gnomAD).

UMPS p.Ala7=

c.21T>C · rs17843775 · VCV342927

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, afr)

Conditions

Oroticaciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -5.2
Overall
CADD	5.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.21% African / African-American · 905/75,026 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0672% 1,085/1,614,154 alleles · low-frequency exomes 537/1,461,872 · genomes 548/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	83
Remaining individualsnot grpmax-eligible	0.08%	1,250
Middle Eastern	0.066%	1,516
Admixed American	0.0633%	1,580
European (non-Finnish)	0.00729%	13,721
South Asian	0.0022%	45,538

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.Ala7=
Coding: c.21T>C
MANE Select: NM_000373
dbSNP: rs17843775
Type: single nucleotide variant
Location: chr3:124730492 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 7: the 'oprtase' region

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

Disease context

Oroticaciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UMPS p.Ala7Pro Uncertain significance ★ ⚠ same residue
UMPS c.*37C>T Uncertain significance ★★ same condition
UMPS p.Ala386= Uncertain significance ★★ same condition
UMPS p.Arg363Gln Uncertain significance ★★ ⚠ same condition
UMPS p.Asp271His Uncertain significance ★★ ⚠ same condition
UMPS c.*1051G>T Benign ★★ same condition
UMPS c.*1211C>A Benign ★★ same condition
UMPS c.*4430C>T 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-ala7 (accessed [today's date]).

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