Is PC c.903+2del pathogenic?

PC c.903+2del is classified Likely pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC c.903+2del?

PC c.903+2del 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 c.903+2del

VCV3633298

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

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	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 0.99
Non-coding constraint	Z 6.08	1 kb window · o/e 0.65 · regional · uncalibrated

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

Variant & gene context

Gene: PC
Coding: c.903+2del
MANE Select: NM_001040716
Type: Deletion
Location: chr11:66870300 (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 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
PC p.Lys1130fs Pathogenic/Likely pathogenic ★★ same condition
PC p.Phe660fs 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-c-903-plus-2del (accessed [today's date]).

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