Is PGK1 p.Ser57= (c.171G>A) pathogenic?

PGK1 p.Ser57= (c.171G>A) is classified Benign/Likely benign in PGK1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). Rare (popmax 0.482%, afr); Associated with glycogen storage disease due to phosphoglycerate kinase 1 deficiency.

What condition is associated with PGK1 p.Ser57= (c.171G>A)?

PGK1 p.Ser57= (c.171G>A) is associated with glycogen storage disease due to phosphoglycerate kinase 1 deficiency (ClinVar).

How common is PGK1 p.Ser57= (c.171G>A) in the general population?

PGK1 p.Ser57= (c.171G>A) is rare (popmax 0.482%, afr) (gnomAD).

PGK1 p.Ser57=

Q: How is Glycogen storage disease due to phosphoglycerate kinase 1 deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.171G>A · rs78165041 · VCV716259

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.482%, afr)

Conditions

glycogen storage disease due to phosphoglycerate kinase 1 deficiency

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 -3.1	GERP -4.2
Overall
CADD	0.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.482% African / African-American · 275/57,095 alleles

Filtering AF 0.435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.417%

Overall 0.0244% 294/1,206,282 alleles · rare exomes 136/1,094,689 · genomes 158/111,593 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.482%	208
Remaining individualsnot grpmax-eligible	0.0232%	4,320
Admixed American	0.00875%	11,426
East Asian	0.00296%	33,752
South Asian	0.00176%	56,706
European (non-Finnish)	0.000224%	445,997

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: PGK1
Protein: p.Ser57=
Coding: c.171G>A
MANE Select: NM_000291
dbSNP: rs78165041
Type: single nucleotide variant
Location: chrX:78113798 (GRCh38)
Structure: AlphaFold pLDDT 96.48 · 30 PDB
Residue 57: a β-strand

Full PGK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to phosphoglycerate kinase 1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood

Similar variants

PGK1 p.Ser57Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PGK1 p.Asp164Val Pathogenic ★★ same condition
PGK1 p.Ala109Asp Uncertain significance ★★ ⚠ same condition
PGK1 p.Ala296Val Uncertain significance ★★ ⚠ same condition
PGK1 p.Ala55Asp Uncertain significance ★★ ⚠ same condition
PGK1 p.Arg151Gln Uncertain significance ★★ same condition
PGK1 p.Arg330Trp Uncertain significance ★★ ⚠ same condition
PGK1 p.Asn163Ser 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/pgk1-p-ser57 (accessed [today's date]).

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