Is PC c.321+19C>G pathogenic?

PC c.321+19C>G is classified Likely benign in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Ultra-rare (popmax 0.0149%, nfe); Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC c.321+19C>G?

PC c.321+19C>G is associated with pyruvate carboxylase deficiency disease (ClinVar).

How common is PC c.321+19C>G in the general population?

PC c.321+19C>G is ultra-rare (popmax 0.0149%, nfe) (gnomAD).

How is Pyruvate carboxylase deficiency inherited?

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

PC c.321+19C>G

rs760426763 · VCV2752823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, nfe)

Conditions

pyruvate carboxylase deficiency disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +19	near-intronic (+19 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -1.3, phastCons 0.005
Non-coding constraint	Z 7.42	1 kb window · o/e 0.58 · regional · uncalibrated
Overall
CADD	5.744	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0149% European (non-Finnish) · 172/1,153,804 alleles

Filtering AF 0.013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0112% 175/1,563,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0149%	6,708
Remaining individualsnot grpmax-eligible	0.0033%	30,279
African / African-American	0.00136%	73,524

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PC
Coding: c.321+19C>G
MANE Select: NM_001040716
dbSNP: rs760426763
Type: single nucleotide variant
Location: chr11:66871668 (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.1368+1G>A Likely pathogenic ★★ same condition
PC c.1826-1G>C Likely pathogenic ★★ same condition
PC c.1983-116C>T Likely pathogenic ★★ same condition
PC c.633+2T>C Likely pathogenic ★★ same condition
PC p.Ala610Thr Pathogenic ★★ same condition
PC p.Ala812Asp Likely pathogenic ★★ same condition
PC p.Arg18Ter Pathogenic/Likely pathogenic ★★ same condition
PC p.Arg263Ter 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-321-plus-19c-g (accessed [today's date]).

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