Is UPB1 p.Pro18= (c.54G>A) pathogenic?

UPB1 p.Pro18= (c.54G>A) is classified Conflicting classifications of pathogenicity in UPB1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0446%, eas); Associated with beta-ureidopropionase deficiency.

What condition is associated with UPB1 p.Pro18= (c.54G>A)?

UPB1 p.Pro18= (c.54G>A) is associated with beta-ureidopropionase deficiency (ClinVar).

How common is UPB1 p.Pro18= (c.54G>A) in the general population?

UPB1 p.Pro18= (c.54G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

How is Beta-ureidopropionase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

UPB1 p.Pro18=

c.54G>A · rs185719774 · VCV902290

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Conditions

beta-ureidopropionase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.154	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -4.3
Overall
CADD	0.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,888 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00533% 86/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
Admixed American	0.00833%	12,004
European (non-Finnish)	0.00492%	20,345
Remaining individualsnot grpmax-eligible	0.0032%	31,255
South Asian	0.0011%	91,082

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: UPB1
Protein: p.Pro18=
Coding: c.54G>A
MANE Select: NM_016327
dbSNP: rs185719774
Type: single nucleotide variant
Location: chr22:24495457 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.10 · 2 PDB

Full UPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

beta-ureidopropionase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Beta-ureidopropionase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

UPB1 p.Pro18Leu Uncertain significance ★ ⚠ same residue
UPB1 c.873+1G>A Pathogenic/Likely pathogenic ★★ same condition
UPB1 c.917-1G>A Pathogenic/Likely pathogenic ★★ same condition
UPB1 p.Asn345Ile Likely pathogenic ★★ same condition
UPB1 p.Gln118Ter Pathogenic ★★ same condition
UPB1 c.-27G>C Uncertain significance ★★ same condition
UPB1 p.Ala2Gly Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg236Gln Uncertain significance ★★ ⚠ 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/upb1-p-pro18 (accessed [today's date]).

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