Is PGAM2 p.Val82Met (c.244G>A) pathogenic?

PGAM2 p.Val82Met (c.244G>A) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-14). AlphaMissense: likely benign (0.2099); Ultra-rare (popmax 0.0223%, eas); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Val82Met (c.244G>A)?

PGAM2 p.Val82Met (c.244G>A) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Val82Met (c.244G>A) in the general population?

PGAM2 p.Val82Met (c.244G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about PGAM2 p.Val82Met (c.244G>A)?

AlphaMissense predicts likely benign (score 0.2099) — an in-silico prediction, not a clinical call.

PGAM2 p.Val82Met

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.244G>A · rs528467394 · VCV959333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.2099	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.72, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	21.5	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 0.0223% East Asian · 10/44,894 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000744% 12/1,613,560 alleles · ultra-rare exomes 9/1,461,308 · genomes 3/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
European (non-Finnish)	0.000169%	590,030

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.Val82Met
Coding: c.244G>A
MANE Select: NM_000290
dbSNP: rs528467394
Type: single nucleotide variant
Location: chr7:44065286 (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-val82met (accessed [today's date]).

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