Is PCCB p.Leu48= (c.144G>C) pathogenic?

PCCB p.Leu48= (c.144G>C) is classified Likely benign in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-05). Very rare (popmax 8.48e-05%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Leu48= (c.144G>C)?

PCCB p.Leu48= (c.144G>C) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Leu48= (c.144G>C) in the general population?

PCCB p.Leu48= (c.144G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Leu48=

c.144G>C · rs1462411928 · VCV1151288

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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
Constraint at this position
Conservation	phyloP 0.67	GERP 1.3, phastCons 0.8
Overall
CADD	9.915	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,768 alleles

Overall 6.2e-05% 1/1,613,036 alleles · very rare exomes 1/1,460,654 · genomes 0/152,382 · joint denominator

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.Leu48=
Coding: c.144G>C
MANE Select: NM_000532
dbSNP: rs1462411928
Type: single nucleotide variant
Location: chr3:136250519 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 48: 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 p.Leu48Arg 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
PCCB c.1499-1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCB c.183+1G>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-leu48 (accessed [today's date]).

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