Is PCK1 p.Ser151= (c.453G>A) pathogenic?

PCK1 p.Ser151= (c.453G>A) is classified Benign in PCK1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 54.2%, mid) — too common for a highly-penetrant pathogenic allele; Associated with phosphoenolpyruvate carboxykinase deficiency, cytosolic.

What condition is associated with PCK1 p.Ser151= (c.453G>A)?

PCK1 p.Ser151= (c.453G>A) is associated with phosphoenolpyruvate carboxykinase deficiency, cytosolic (ClinVar).

How is Phosphoenolpyruvate carboxykinase deficiency inherited?

Typically Autosomal recessive, Mitochondrial inheritance (Orphanet). A genetic counselor can assess individual risk for a family.

PCK1 p.Ser151=

Q: How common is PCK1 p.Ser151= (c.453G>A) in the general population?

PCK1 p.Ser151= (c.453G>A) is common (popmax 54.2%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.453G>A · rs1062600 · VCV338875

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 54.2%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

phosphoenolpyruvate carboxykinase deficiency, cytosolic

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 -8.5	GERP -4.5
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 54.2% Middle Eastern · 3,249/5,998 alleles

Filtering AF 52.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 52%

Overall 43% 691,806/1,610,092 alleles · common exomes 632,210/1,458,062 · genomes 59,596/152,030 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	54.6%	2
Middle Easterngrpmax	54.2%	2
European (non-Finnish)	46%	2
Finnishnot grpmax-eligible	45%	2
Ashkenazi Jewishnot grpmax-eligible	44.6%	2
Remaining individualsnot grpmax-eligible	42.1%	2
South Asian	38.9%	3
African / African-American	33.2%	3
Admixed American	27.9%	4
East Asian	3.32%	30

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PCK1
Protein: p.Ser151=
Coding: c.453G>A
MANE Select: NM_002591
dbSNP: rs1062600
Type: single nucleotide variant
Location: chr20:57562742 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.60 · 7 PDB

Full PCK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

phosphoenolpyruvate carboxykinase deficiency, cytosolic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Phosphoenolpyruvate carboxykinase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance
Onset: Infancy, Neonatal

Similar variants

PCK1 p.Ser151Leu Uncertain significance ★ same residue
PCK1 p.Ser151Thr Uncertain significance ★ same residue
PCK1 c.*361G>A Uncertain significance ★★ same condition
PCK1 p.Ala319Thr Uncertain significance ★★ ⚠ same condition
PCK1 p.Ala563Val Uncertain significance ★★ ⚠ same condition
PCK1 p.Arg68Leu Uncertain significance ★★ ⚠ same condition
PCK1 p.Asn403Asp Uncertain significance ★★ ⚠ same condition
PCK1 p.Cys245Gly Uncertain significance ★★ ⚠ 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/pck1-p-ser151 (accessed [today's date]).

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