Is PC p.Ser293= (c.879C>T) pathogenic?

PC p.Ser293= (c.879C>T) is classified Conflicting classifications of pathogenicity in PC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-10). Low-frequency (popmax 1.11%, eas); Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC p.Ser293= (c.879C>T)?

PC p.Ser293= (c.879C>T) is associated with pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Ser293= (c.879C>T) in the general population?

PC p.Ser293= (c.879C>T) is low-frequency (popmax 1.11%, eas) (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.Ser293=

c.879C>T · rs183131461 · VCV305631

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, eas)

Conditions

pyruvate carboxylase deficiency disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.6
Overall
CADD	4.999	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.11% East Asian · 497/44,878 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.995%

Overall 0.0323% 521/1,613,444 alleles · low-frequency exomes 496/1,461,230 · genomes 25/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.11%	90
Finnishnot grpmax-eligible	0.0252%	3,964
Middle Eastern	0.0166%	6,038
Remaining individualsnot grpmax-eligible	0.0064%	15,624
Admixed American	0.00167%	60,028
African / African-American	0.00133%	75,006
European (non-Finnish)	8.47e-05%	1,179,984

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
Protein: p.Ser293=
Coding: c.879C>T
MANE Select: NM_001040716
dbSNP: rs183131461
Type: single nucleotide variant
Location: chr11:66870326 (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 293: 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 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-p-ser293 (accessed [today's date]).

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