Is PCCB p.Ala497= (c.1491A>C) pathogenic?

PCCB p.Ala497= (c.1491A>C) is classified Likely benign in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). Absent from gnomAD v4.1; Associated with propionic acidemia.

What condition is associated with PCCB p.Ala497= (c.1491A>C)?

PCCB p.Ala497= (c.1491A>C) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Ala497= (c.1491A>C) in the general population?

PCCB p.Ala497= (c.1491A>C) is absent from gnomAD v4.1 (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Ala497=

c.1491A>C · rs2529977543 · VCV2848102

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.4	GERP -4.7
Overall
CADD	5.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PCCB
Protein: p.Ala497=
Coding: c.1491A>C
MANE Select: NM_000532
dbSNP: rs2529977543
Type: single nucleotide variant
Location: chr3:136328850 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 497: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region; a UniProt-annotated variant site (in pa-2; does not affect either heteromeric or homomeric assembly; decreased thermostability affecting holoenzyme oligomerization; no effect on propionyl-coa carboxylase activity); 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.Ala497Val Benign/Likely benign ★★ same residue
PCCB p.Ala497Gly Uncertain significance ★ ⚠ same residue
PCCB p.Ala497Thr Uncertain significance ★ ⚠ 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

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-ala497 (accessed [today's date]).

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