Is PCCB p.Ser187= (c.561C>T) pathogenic?

PCCB p.Ser187= (c.561C>T) is classified Conflicting classifications of pathogenicity in PCCB (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0187%, sas); Associated with propionic acidemia.

What condition is associated with PCCB p.Ser187= (c.561C>T)?

PCCB p.Ser187= (c.561C>T) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Ser187= (c.561C>T) in the general population?

PCCB p.Ser187= (c.561C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Ser187=

c.561C>T · rs145057852 · VCV671659

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4
Overall
CADD	5.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,044 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0121% 195/1,612,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,356
European (non-Finnish)	0.0138%	7,233
Remaining individualsnot grpmax-eligible	0.0128%	7,805
East Asian	0.00891%	11,220
African / African-American	0.00267%	37,510
Admixed American	0.00167%	60,024

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.Ser187=
Coding: c.561C>T
MANE Select: NM_000532
dbSNP: rs145057852
Type: single nucleotide variant
Location: chr3:136283854 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 187: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region; a turn

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-ser187 (accessed [today's date]).

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