Is UMPS p.Pro115Ser (c.343C>T) pathogenic?

UMPS p.Pro115Ser (c.343C>T) is classified Uncertain significance in UMPS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-07). AlphaMissense: likely benign (0.0908); Ultra-rare (popmax 0.012%, afr); Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Pro115Ser (c.343C>T)?

UMPS p.Pro115Ser (c.343C>T) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Pro115Ser (c.343C>T) in the general population?

UMPS p.Pro115Ser (c.343C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about UMPS p.Pro115Ser (c.343C>T)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

UMPS p.Pro115Ser

c.343C>T · rs779723295 · VCV1483728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hereditary orotic aciduria, type 1

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.016 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,872 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00062% 10/1,613,930 alleles · ultra-rare exomes 5/1,461,884 · genomes 5/152,046 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,319
European (non-Finnish)	8.47e-05%	1,180,038

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.Pro115Ser
Coding: c.343C>T
MANE Select: NM_000373
dbSNP: rs779723295
Type: single nucleotide variant
Location: chr3:124737600 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 115: the 'oprtase' 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.Pro115Leu Uncertain significance ★ ⚠ same residue
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

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-pro115ser (accessed [today's date]).

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