Is PGAM2 p.Arg40Gln (c.119G>A) pathogenic?

PGAM2 p.Arg40Gln (c.119G>A) is classified Conflicting classifications of pathogenicity in PGAM2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-11-20). AlphaMissense: likely benign (0.111); Ultra-rare (popmax 0.0498%, nfe); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Arg40Gln (c.119G>A)?

PGAM2 p.Arg40Gln (c.119G>A) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Arg40Gln (c.119G>A) in the general population?

PGAM2 p.Arg40Gln (c.119G>A) is ultra-rare (popmax 0.0498%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Arg40Gln (c.119G>A)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

PGAM2 p.Arg40Gln

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.119G>A · rs140545494 · VCV529224

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0498%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -7.99	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 0.57	GERP 0.68
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0498% European (non-Finnish) · 588/1,180,050 alleles

Filtering AF 0.0464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0451%

Overall 0.0402% 649/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0498%	2,007
Remaining individualsnot grpmax-eligible	0.0304%	3,289
Finnishnot grpmax-eligible	0.0297%	3,366
African / African-American	0.0187%	5,354
Admixed American	0.0117%	8,573
South Asian	0.0022%	45,544

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.Arg40Gln
Coding: c.119G>A
MANE Select: NM_000290
dbSNP: rs140545494
Type: single nucleotide variant
Location: chr7:44065411 (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.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-arg40gln (accessed [today's date]).

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