Is PGAM2 p.Ala48Val (c.143C>T) pathogenic?

PGAM2 p.Ala48Val (c.143C>T) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.2329); Very rare (popmax 0.000254%, nfe); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Ala48Val (c.143C>T)?

PGAM2 p.Ala48Val (c.143C>T) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Ala48Val (c.143C>T) in the general population?

PGAM2 p.Ala48Val (c.143C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Ala48Val (c.143C>T)?

AlphaMissense predicts likely benign (score 0.2329) — an in-silico prediction, not a clinical call.

PGAM2 p.Ala48Val

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.143C>T · rs1308236739 · VCV847748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2329	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -12.86	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	25.4	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 0.000254% European (non-Finnish) · 3/1,180,048 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,906 alleles · very rare exomes 1/1,461,684 · genomes 2/152,222 · joint denominator

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.Ala48Val
Coding: c.143C>T
MANE Select: NM_000290
dbSNP: rs1308236739
Type: single nucleotide variant
Location: chr7:44065387 (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-ala48val (accessed [today's date]).

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