Is PGAM2 p.Leu224= (c.670C>T) pathogenic?

PGAM2 p.Leu224= (c.670C>T) is classified Likely benign in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Absent from gnomAD v4.1; Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Leu224= (c.670C>T)?

PGAM2 p.Leu224= (c.670C>T) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Leu224= (c.670C>T) in the general population?

PGAM2 p.Leu224= (c.670C>T) is absent from gnomAD v4.1 (gnomAD).

PGAM2 p.Leu224=

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

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

c.670C>T · VCV4710722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glycogen storage disease due to phosphoglycerate mutase 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 5.1	GERP -0.46, phastCons 1
Overall
CADD	9.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PGAM2
Protein: p.Leu224=
Coding: c.670C>T
MANE Select: NM_000290
Type: single nucleotide variant
Location: chr7:44062856 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.07

Full PGAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

PGAM2 p.Arg86Cys Uncertain significance ★★ ⚠ same condition
PGAM2 p.Lys39Gln Uncertain significance ★★ ⚠ same condition
PGAM2 p.Gln111Ter Pathogenic ★ same condition
PGAM2 p.Trp78Ter Pathogenic ★ same condition
PGAM2 p.Ala204Val Uncertain significance ★ ⚠ same condition
PGAM2 p.Arg40Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
PGAM2 p.Arg5Cys Uncertain significance ★ ⚠ same condition
PGAM2 p.Arg65Cys 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/pgam2-p-leu224 (accessed [today's date]).

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