Is PC p.Glu1046fs (c.3137_3138del) pathogenic?

PC p.Glu1046fs (c.31373138del) is classified Pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). Absent from gnomAD; Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC p.Glu1046fs (c.3137_3138del)?

PC p.Glu1046fs (c.3137_3138del) is associated with pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Glu1046fs (c.3137_3138del) in the general population?

PC p.Glu1046fs (c.3137_3138del) is absent from gnomAD (gnomAD).

How is Pyruvate carboxylase deficiency inherited?

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

PC p.Glu1046fs

c.3137_3138del · rs2495399570 · VCV2803769

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

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 21 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	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: PC
Protein: p.Glu1046fs
Coding: c.3137_3138del
MANE Select: NM_001040716
dbSNP: rs2495399570
Type: Microsatellite
Location: chr11:66849620 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB

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.Glu1046Gly Uncertain significance ★ ⚠ same residue
PC p.Val831_Phe832insTer Pathogenic ★★ same condition
PC c.2224-31TC[8] Benign/Likely benign ★★ same condition
PC p.Ala125fs Pathogenic ★ same condition
PC p.Asn669fs Pathogenic ★ same condition
PC p.Glu664fs Likely pathogenic ★ same condition
PC p.Ser705fs Likely pathogenic ★ same condition
PC p.Val582fs 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-glu1046fs (accessed [today's date]).

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