Is PGAM2 p.Lys39Gln (c.115A>C) pathogenic?

PGAM2 p.Lys39Gln (c.115A>C) is classified Uncertain significance in PGAM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-26). AlphaMissense: likely benign (0.0936); Ultra-rare (popmax 0.0176%, nfe); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Lys39Gln (c.115A>C)?

PGAM2 p.Lys39Gln (c.115A>C) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Lys39Gln (c.115A>C) in the general population?

PGAM2 p.Lys39Gln (c.115A>C) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Lys39Gln (c.115A>C)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

PGAM2 p.Lys39Gln

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.115A>C · rs147126221 · VCV909252

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP 0.87, phastCons 0.031
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	17.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0176% European (non-Finnish) · 208/1,180,054 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0137% 221/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0176%	5,673
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00666%	15,004
Finnishnot grpmax-eligible	0.00156%	63,978
African / African-American	0.00133%	74,932
South Asian	0.0011%	91,090

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: PGAM2
Protein: p.Lys39Gln
Coding: c.115A>C
MANE Select: NM_000290
dbSNP: rs147126221
Type: single nucleotide variant
Location: chr7:44065415 (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.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
PGAM2 p.Gly144Asp 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-lys39gln (accessed [today's date]).

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