Is PC p.Gly87Ser (c.259G>A) pathogenic?

PC p.Gly87Ser (c.259G>A) is classified Uncertain significance in PC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.7987); Ultra-rare (popmax 0.0284%, amr); Associated with pyruvate carboxylase deficiency disease.

What condition is associated with PC p.Gly87Ser (c.259G>A)?

PC p.Gly87Ser (c.259G>A) is associated with pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Gly87Ser (c.259G>A) in the general population?

PC p.Gly87Ser (c.259G>A) is ultra-rare (popmax 0.0284%, amr) (gnomAD).

How is Pyruvate carboxylase deficiency inherited?

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

What do computational predictors say about PC p.Gly87Ser (c.259G>A)?

AlphaMissense predicts likely pathogenic (score 0.7987) — an in-silico prediction, not a clinical call.

PC p.Gly87Ser

c.259G>A · rs770055702 · VCV2050548

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pyruvate carboxylase deficiency disease

Computational evidence

Protein change
AlphaMissense	0.7987	likely pathogenic
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -13.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% Admixed American · 16/56,282 alleles

Filtering AF 0.0178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.00239% 38/1,590,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0284%	3,518
Middle Eastern	0.0165%	6,060
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,086
Remaining individualsnot grpmax-eligible	0.00325%	30,805
European (non-Finnish)	0.00154%	64,943

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.Gly87Ser
Coding: c.259G>A
MANE Select: NM_001040716
dbSNP: rs770055702
Type: single nucleotide variant
Location: chr11:66871749 (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 87: 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.Gly87Arg Uncertain significance ★ ⚠ same residue
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

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-gly87ser (accessed [today's date]).

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