Is PC p.Gln286fs (c.854dup) pathogenic?

PC p.Gln286fs (c.854dup) is classified Likely pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC p.Gln286fs (c.854dup)?

PC p.Gln286fs (c.854dup) is associated with pyruvate carboxylase deficiency disease (ClinVar).

How is Pyruvate carboxylase deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PC p.Gln286fs

c.854dup · VCV3600149

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pyruvate carboxylase deficiency disease

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 9 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -4, phastCons 1

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

Variant & gene context

Gene: PC
Protein: p.Gln286fs
Coding: c.854dup
MANE Select: NM_001040716
Type: Duplication
Location: chr11:66870350 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB
Residue 286: the biotin carboxylation domain; the atp-grasp domain; an α-helix

Full PC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pyruvate carboxylase deficiency disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pyruvate carboxylase deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PC p.Ala787fs Likely pathogenic ★ same condition
PC p.Asn110fs Likely pathogenic ★ same condition
PC p.Asn864fs Likely pathogenic ★ same condition
PC p.Asp390fs Pathogenic ★ same condition
PC p.Asp916fs Pathogenic ★ same condition
PC p.Glu1146fs Likely pathogenic ★ same condition
PC p.Glu123Ter Pathogenic ★ same condition
PC p.Gly150dup 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/pc-p-gln286fs (accessed [today's date]).

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