Is PCCB p.Lys60= (c.180G>A) pathogenic?

PCCB p.Lys60= (c.180G>A) is classified Conflicting classifications of pathogenicity in PCCB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-01). Rare (popmax 0.105%, afr); Associated with propionic acidemia.

What condition is associated with PCCB p.Lys60= (c.180G>A)?

PCCB p.Lys60= (c.180G>A) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Lys60= (c.180G>A) in the general population?

PCCB p.Lys60= (c.180G>A) is rare (popmax 0.105%, afr) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Lys60=

c.180G>A · rs140636870 · VCV706453

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, afr)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP -0.66, phastCons 1
Overall
CADD	12.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% African / African-American · 79/74,922 alleles

Filtering AF 0.0867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0798%

Overall 0.00571% 92/1,611,754 alleles · rare exomes 51/1,459,502 · genomes 41/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.105%	948
Admixed American	0.01%	9,983
Remaining individualsnot grpmax-eligible	0.00962%	10,393
European (non-Finnish)	8.48e-05%	1,179,485

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.Lys60=
Coding: c.180G>A
MANE Select: NM_000532
dbSNP: rs140636870
Type: single nucleotide variant
Location: chr3:136250555 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 60: 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.Lys60_Arg61delinsAsnTer Pathogenic ★ same residue
PCCB p.Lys60Ter 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

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-lys60 (accessed [today's date]).

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