Is PC p.Ala412fs (c.1234_1240del) pathogenic?

PC p.Ala412fs (c.12341240del) is classified Pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-26). Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC p.Ala412fs (c.1234_1240del)?

PC p.Ala412fs (c.1234_1240del) 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.Ala412fs

c.1234_1240del · VCV3776280

Pathogenic Single submitter

Classification

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 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Variant & gene context

Gene: PC
Protein: p.Ala412fs
Coding: c.1234_1240del
MANE Select: NM_001040716
Type: Deletion
Location: chr11:66863902 (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 412: the biotin carboxylation domain

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.Ala412Thr Uncertain significance ★★ ⚠ same residue
PC p.Ala412= Likely benign ★ same residue
PC c.2473+2_2473+5del Pathogenic/Likely pathogenic ★★ same condition
PC p.Arg571fs Pathogenic/Likely pathogenic ★★ same condition
PC p.Cys752fs Pathogenic/Likely pathogenic ★★ same condition
PC p.Gly303fs Pathogenic/Likely pathogenic ★★ same condition
PC p.Leu1030fs Pathogenic/Likely pathogenic ★★ same condition
PC p.Leu1137fs 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/pc-p-ala412fs (accessed [today's date]).

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