Is UPB1 p.Phe282= (c.846C>T) pathogenic?

UPB1 p.Phe282= (c.846C>T) is classified Benign in UPB1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.76%, afr); Associated with beta-ureidopropionase deficiency.

What condition is associated with UPB1 p.Phe282= (c.846C>T)?

UPB1 p.Phe282= (c.846C>T) is associated with beta-ureidopropionase deficiency (ClinVar).

How common is UPB1 p.Phe282= (c.846C>T) in the general population?

UPB1 p.Phe282= (c.846C>T) is low-frequency (popmax 2.76%, afr) (gnomAD).

How is Beta-ureidopropionase deficiency inherited?

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

UPB1 p.Phe282=

c.846C>T · rs2232867 · VCV100160

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.76%, afr)

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 -0.14	GERP 0.31, phastCons 0.44
Overall
CADD	8.175	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.76% African / African-American · 2,072/75,066 alleles

Filtering AF 2.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.62%

Overall 0.146% 2,355/1,614,162 alleles · low-frequency exomes 1,163/1,461,820 · genomes 1,192/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.76%	36
Admixed American	0.185%	541
Remaining individualsnot grpmax-eligible	0.174%	573
Middle Eastern	0.099%	1,010
South Asian	0.00988%	10,120
European (non-Finnish)	0.00398%	25,107
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Phe282=
Coding: c.846C>T
MANE Select: NM_016327
dbSNP: rs2232867
Type: single nucleotide variant
Location: chr22:24520441 (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 282: the cn hydrolase domain; a β-strand

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 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
UPB1 p.Arg68Gln 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-phe282 (accessed [today's date]).

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