Is PCCB p.Arg26fs (c.76dup) pathogenic?

PCCB p.Arg26fs (c.76dup) is classified Pathogenic in PCCB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-22). Very rare (popmax 8.5e-05%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Arg26fs (c.76dup)?

PCCB p.Arg26fs (c.76dup) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Arg26fs (c.76dup) in the general population?

PCCB p.Arg26fs (c.76dup) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Arg26fs

c.76dup · rs1941479615 · VCV944298

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, 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 1 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.4	GERP -4.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,078 alleles

Overall 6.23e-05% 1/1,604,968 alleles · very rare exomes 1/1,452,610 · genomes 0/152,358 · 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.Arg26fs
Coding: c.76dup
MANE Select: NM_000532
dbSNP: rs1941479615
Type: Duplication
Location: chr3:136250449 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB

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.Arg26= Likely benign ★ same residue
PCCB p.Ala164fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Glu421Ter Pathogenic ★★ same condition
PCCB p.Leu280fs Pathogenic ★★ same condition
PCCB p.Thr150fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Thr185fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Val217fs Pathogenic ★★ same condition
PCCB p.Val392fs 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-arg26fs (accessed [today's date]).

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