Is PGAM2 p.Ser31Arg (c.93T>G) pathogenic?

PGAM2 p.Ser31Arg (c.93T>G) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-25). AlphaMissense: likely pathogenic (0.9894); Absent from gnomAD v4.1; Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Ser31Arg (c.93T>G)?

PGAM2 p.Ser31Arg (c.93T>G) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Ser31Arg (c.93T>G) in the general population?

PGAM2 p.Ser31Arg (c.93T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAM2 p.Ser31Arg (c.93T>G)?

AlphaMissense predicts likely pathogenic (score 0.9894) — an in-silico prediction, not a clinical call.

PGAM2 p.Ser31Arg

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.93T>G · rs2128796719 · VCV2010719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9894 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.9894	likely pathogenic
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -15.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ser31Arg
Coding: c.93T>G
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs2128796719
Type: single nucleotide variant
Location: chr7:44065437 (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-ser31arg (accessed [today's date]).

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