Is PCCB c.*91C>A pathogenic?

PCCB c.91C>A is classified Uncertain significance in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.177%, afr); Associated with propionic acidemia.

What condition is associated with PCCB c.*91C>A?

PCCB c.*91C>A is associated with propionic acidemia (ClinVar).

How common is PCCB c.*91C>A in the general population?

PCCB c.*91C>A is rare (popmax 0.177%, afr) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB c.*91C>A

rs115533065 · VCV343481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.177%, 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 -0.005	GERP -0.6
Non-coding constraint	Z 0.32	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	4.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.177% African / African-American · 132/74,742 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.0115% 184/1,602,780 alleles · rare exomes 87/1,450,472 · genomes 97/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.177%	566
Remaining individualsnot grpmax-eligible	0.0371%	2,697
Middle Eastern	0.0166%	6,034
Admixed American	0.00334%	29,910
European (non-Finnish)	0.00222%	45,113

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
Coding: c.*91C>A
MANE Select: NM_000532
dbSNP: rs115533065
Type: single nucleotide variant
Location: chr3:136330117 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB

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-c-star-91c-a (accessed [today's date]).

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