Is UPB1 p.Ser264= (c.792C>T) pathogenic?

UPB1 p.Ser264= (c.792C>T) is classified Conflicting classifications of pathogenicity in UPB1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-03). Ultra-rare (popmax 0.0139%, nfe); Associated with beta-ureidopropionase deficiency.

What condition is associated with UPB1 p.Ser264= (c.792C>T)?

UPB1 p.Ser264= (c.792C>T) is associated with beta-ureidopropionase deficiency (ClinVar).

How common is UPB1 p.Ser264= (c.792C>T) in the general population?

UPB1 p.Ser264= (c.792C>T) is ultra-rare (popmax 0.0139%, nfe) (gnomAD).

How is Beta-ureidopropionase deficiency inherited?

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

UPB1 p.Ser264=

c.792C>T · rs145766755 · VCV900674

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, nfe)

Conditions

beta-ureidopropionase deficiency

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 -7.9	GERP -2.7
Overall
CADD	0.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0139% European (non-Finnish) · 164/1,180,008 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0124% 200/1,614,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0375%	2,667
European (non-Finnish)grpmax	0.0139%	7,195
Remaining individualsnot grpmax-eligible	0.0112%	8,926
Admixed American	0.00333%	30,002
South Asian	0.0022%	45,533
African / African-American	0.00133%	74,938

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser264=
Coding: c.792C>T
MANE Select: NM_016327
dbSNP: rs145766755
Type: single nucleotide variant
Location: chr22:24520387 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.10 · 2 PDB
Residue 264: the cn hydrolase domain; a UniProt-annotated variant site (in upb1d; complete loss of activity); an α-helix

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.Ser264Arg Conflicting classifications of pathogenicity ★ ⚠ 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-ser264 (accessed [today's date]).

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