Is PCCB p.Val25fs (c.73del) pathogenic?

PCCB p.Val25fs (c.73del) is classified Pathogenic in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). Associated with propionic acidemia.

What condition is associated with PCCB p.Val25fs (c.73del)?

PCCB p.Val25fs (c.73del) is associated with propionic acidemia (ClinVar).

How is Propionic acidemia inherited?

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

PCCB p.Val25fs

c.73del · VCV3662598

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 -0.19	GERP -3.6

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

Variant & gene context

Gene: PCCB
Protein: p.Val25fs
Coding: c.73del
MANE Select: NM_000532
Type: Deletion
Location: chr3:136250447 (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.Val25Ile Uncertain significance ★★ ⚠ same residue
PCCB p.Val25= 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
PCCB p.Ile408fs 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-val25fs (accessed [today's date]).

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