Is PCCB p.Leu210= (c.630A>C) pathogenic?

PCCB p.Leu210= (c.630A>C) is classified Likely benign in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.00229%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Leu210= (c.630A>C)?

PCCB p.Leu210= (c.630A>C) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Leu210= (c.630A>C) in the general population?

PCCB p.Leu210= (c.630A>C) is very rare (popmax 0.00229%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Leu210=

c.630A>C · rs1269554950 · VCV1116497

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00229%, 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 -0.26	GERP -4, phastCons 0.002
Overall
CADD	3.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,178,092 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00192% 28/1,459,622 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,633
Remaining individualsnot grpmax-eligible	0.0016%	62,420

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.Leu210=
Coding: c.630A>C
MANE Select: NM_000532
dbSNP: rs1269554950
Type: single nucleotide variant
Location: chr3:136283923 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 210: 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.Leu210fs 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
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-leu210 (accessed [today's date]).

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