Is PGK1 p.Val303= (c.909G>C) pathogenic?

PGK1 p.Val303= (c.909G>C) is classified Benign/Likely benign in PGK1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-21). Rare (popmax 0.314%, afr); Associated with Inborn genetic diseases.

What condition is associated with PGK1 p.Val303= (c.909G>C)?

PGK1 p.Val303= (c.909G>C) is associated with Inborn genetic diseases, glycogen storage disease due to phosphoglycerate kinase 1 deficiency (ClinVar).

How common is PGK1 p.Val303= (c.909G>C) in the general population?

PGK1 p.Val303= (c.909G>C) is rare (popmax 0.314%, afr) (gnomAD).

PGK1 p.Val303=

c.909G>C · rs142525614 · VCV793410

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.314%, afr)

Conditions

Inborn genetic diseases

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 2.8	GERP -1.4, phastCons 1
Overall
CADD	6.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% African / African-American · 180/57,333 alleles

Filtering AF 0.276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.262%

Overall 0.0151% 183/1,208,690 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.314%	319
Admixed American	0.00218%	45,813
Remaining individualsnot grpmax-eligible	0.0021%	47,561
European (non-Finnish)	0.000112%	893,863

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.Val303=
Coding: c.909G>C
MANE Select: NM_000291
dbSNP: rs142525614
Type: single nucleotide variant
Location: chrX:78123347 (GRCh38)
Structure: AlphaFold pLDDT 96.48 · 30 PDB
Residue 303: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease due to phosphoglycerate kinase 1 deficiency

Similar variants

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.Asn110Thr 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-val303 (accessed [today's date]).

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