Is PCCB p.Pro294= (c.882C>T) pathogenic?

PCCB p.Pro294= (c.882C>T) is classified Conflicting classifications of pathogenicity in PCCB (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-26). Rare (popmax 0.147%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Pro294= (c.882C>T)?

PCCB p.Pro294= (c.882C>T) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Pro294= (c.882C>T) in the general population?

PCCB p.Pro294= (c.882C>T) is rare (popmax 0.147%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Pro294=

c.882C>T · rs142730126 · VCV343472

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, nfe)

Conditions

propionic acidemia

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
Pangolin	Δ0.32	gain · loss 0.10 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.97, phastCons 1
Overall
CADD	18.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% European (non-Finnish) · 1,737/1,179,976 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.122% 1,966/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.147%	679
Remaining individualsnot grpmax-eligible	0.115%	868
South Asian	0.0933%	1,071
Admixed American	0.0583%	1,715
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
Finnishnot grpmax-eligible	0.0203%	4,926
African / African-American	0.02%	5,004

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: PCCB
Protein: p.Pro294=
Coding: c.882C>T
MANE Select: NM_000532
dbSNP: rs142730126
Type: single nucleotide variant
Location: chr3:136298070 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 294: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region

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

Disease context

propionic acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Propionic acidemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: >1 / 1000 (Canada)

Similar variants

PCCB c.1199-1G>A Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1199-2A>G Pathogenic ★★ same condition
PCCB c.1398+1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1398+1G>T Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1498+2T>C Pathogenic ★★ same condition
PCCB c.1499-1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCB c.183+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCCB c.183+5G>A Pathogenic/Likely pathogenic ★★ 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/pccb-p-pro294 (accessed [today's date]).

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