Is PCCB p.Pro285= (c.855G>A) pathogenic?

PCCB p.Pro285= (c.855G>A) is classified Likely benign in PCCB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00934%, afr); Associated with propionic acidemia.

What condition is associated with PCCB p.Pro285= (c.855G>A)?

PCCB p.Pro285= (c.855G>A) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Pro285= (c.855G>A) in the general population?

PCCB p.Pro285= (c.855G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Pro285=

c.855G>A · rs982512877 · VCV754992

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

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
Constraint at this position
Conservation	phyloP -4.9	GERP -3.6
Overall
CADD	0.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,912 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000867% 14/1,613,990 alleles · very rare exomes 10/1,461,838 · genomes 4/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,702
Admixed American	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000339%	295,004

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.Pro285=
Coding: c.855G>A
MANE Select: NM_000532
dbSNP: rs982512877
Type: single nucleotide variant
Location: chr3:136298043 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 285: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region; an α-helix

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 p.Pro285Leu Uncertain significance ★★ ⚠ same residue
PCCB p.Pro285fs Likely pathogenic ★ same residue
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

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-pro285 (accessed [today's date]).

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