Is UMPS p.Ala165= (c.495G>A) pathogenic?

UMPS p.Ala165= (c.495G>A) is classified Conflicting classifications of pathogenicity in UMPS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-05). Rare (popmax 0.372%, eas); Associated with Oroticaciduria.

What condition is associated with UMPS p.Ala165= (c.495G>A)?

UMPS p.Ala165= (c.495G>A) is associated with Oroticaciduria (ClinVar).

How common is UMPS p.Ala165= (c.495G>A) in the general population?

UMPS p.Ala165= (c.495G>A) is rare (popmax 0.372%, eas) (gnomAD).

UMPS p.Ala165=

c.495G>A · rs75971351 · VCV784598

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.372%, eas)

Conditions

Oroticaciduria

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 -6.8	GERP -5.5
Overall
CADD	0.189	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.372% East Asian · 167/44,888 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.319%

Overall 0.0313% 506/1,614,178 alleles · rare exomes 332/1,461,888 · genomes 174/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.372%	269
African / African-American	0.369%	271
Admixed American	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Finnishnot grpmax-eligible	0.00312%	32,016
European (non-Finnish)	0.00144%	69,413
South Asian	0.0011%	91,070

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.Ala165=
Coding: c.495G>A
MANE Select: NM_000373
dbSNP: rs75971351
Type: single nucleotide variant
Location: chr3:124737752 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 165: the 'oprtase' region; a turn

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.Ala165Val 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-ala165 (accessed [today's date]).

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