Is UMPS p.Ala6= (c.18A>G) pathogenic?

UMPS p.Ala6= (c.18A>G) is classified Benign/Likely benign in UMPS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-23). Rare (popmax 0.576%, afr); Associated with Oroticaciduria.

What condition is associated with UMPS p.Ala6= (c.18A>G)?

UMPS p.Ala6= (c.18A>G) is associated with Oroticaciduria (ClinVar).

How common is UMPS p.Ala6= (c.18A>G) in the general population?

UMPS p.Ala6= (c.18A>G) is rare (popmax 0.576%, afr) (gnomAD).

UMPS p.Ala6=

c.18A>G · rs141501397 · VCV342926

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.576%, 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 -4.9	GERP -5.2
Overall
CADD	0.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% African / African-American · 432/75,046 alleles

Filtering AF 0.531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.513%

Overall 0.0303% 489/1,614,170 alleles · rare exomes 232/1,461,850 · genomes 257/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.576%	174
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Admixed American	0.0416%	2,401
South Asian	0.0011%	91,086
European (non-Finnish)	0.000169%	590,002

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.Ala6=
Coding: c.18A>G
MANE Select: NM_000373
dbSNP: rs141501397
Type: single nucleotide variant
Location: chr3:124730489 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 6: 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 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
UMPS c.*725A>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-ala6 (accessed [today's date]).

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