Is PCCB p.Val378fs (c.1131dup) pathogenic?

PCCB p.Val378fs (c.1131dup) is classified Pathogenic in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). No gnomAD frequency available for this variant; Associated with propionic acidemia.

What condition is associated with PCCB p.Val378fs (c.1131dup)?

PCCB p.Val378fs (c.1131dup) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Val378fs (c.1131dup) in the general population?

PCCB p.Val378fs (c.1131dup) is no gnomAD frequency available for this variant (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Val378fs

c.1131dup · rs2529970405 · VCV2780029

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 11	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PCCB
Protein: p.Val378fs
Coding: c.1131dup
MANE Select: NM_000532
dbSNP: rs2529970405
Type: Duplication
Location: chr3:136326839 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 378: the coa carboxyltransferase c-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.Val378Ile Uncertain significance ★★ ⚠ same residue
PCCB p.Val378Leu Uncertain significance ★ ⚠ same residue
PCCB p.Val378Phe Uncertain significance ★ ⚠ same residue
PCCB p.Val378= Likely benign ★ same residue
PCCB p.Ala164fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Arg26fs Pathogenic ★★ same condition
PCCB p.Glu421Ter Pathogenic ★★ same condition
PCCB p.Leu280fs 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-val378fs (accessed [today's date]).

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