Is PCCB p.Phe391fs (c.1172_1173del) pathogenic?

PCCB p.Phe391fs (c.11721173del) is classified Pathogenic in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-04). Very rare (popmax 0.00017%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Phe391fs (c.1172_1173del)?

PCCB p.Phe391fs (c.1172_1173del) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Phe391fs (c.1172_1173del) in the general population?

PCCB p.Phe391fs (c.1172_1173del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Phe391fs

c.1172_1173del · rs587776758 · VCV659170

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,150 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,134 alleles · very rare exomes 2/1,459,820 · genomes 0/152,314 · 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.Phe391fs
Coding: c.1172_1173del
MANE Select: NM_000532
dbSNP: rs587776758
Type: Deletion
Location: chr3:136326882 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 391: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region; a β-strand

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.Phe391Ser Pathogenic/Likely pathogenic ★★ same residue
PCCB p.Phe391Cys Likely pathogenic ★ same residue
PCCB p.Phe391= Likely benign ★ same residue
PCCB c.1091-8_1091-3del Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1399-2_1399-1del Pathogenic/Likely pathogenic ★★ same condition
PCCB c.155_183+17del Pathogenic/Likely pathogenic ★★ same condition
PCCB c.187_203del Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Gln124fs 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-phe391fs (accessed [today's date]).

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