Is PGAM2 p.Glu236Ala (c.707A>C) pathogenic?

PGAM2 p.Glu236Ala (c.707A>C) is classified Conflicting classifications of pathogenicity in PGAM2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1152); Low-frequency (popmax 1.25%, mid); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Glu236Ala (c.707A>C)?

PGAM2 p.Glu236Ala (c.707A>C) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Glu236Ala (c.707A>C) in the general population?

PGAM2 p.Glu236Ala (c.707A>C) is low-frequency (popmax 1.25%, mid) (gnomAD).

What do computational predictors say about PGAM2 p.Glu236Ala (c.707A>C)?

AlphaMissense predicts likely benign (score 0.1152) — an in-silico prediction, not a clinical call.

PGAM2 p.Glu236Ala

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.707A>C · rs140230479 · VCV440991

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1152 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.1152	likely benign
REVEL	0.543	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	24.4	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 1.25% Middle Eastern · 76/6,062 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.943%

Overall 0.0459% 741/1,614,202 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.25%	80
South Asian	0.397%	252
Remaining individualsnot grpmax-eligible	0.0656%	1,525
European (non-Finnish)	0.0211%	4,739
Admixed American	0.01%	10,005
Finnishnot grpmax-eligible	0.00781%	12,807
African / African-American	0.00267%	37,520

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.Glu236Ala
Coding: c.707A>C
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs140230479
Type: single nucleotide variant
Location: chr7:44062819 (GRCh38)

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

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-glu236ala (accessed [today's date]).

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