Is PGAM2 p.His186= (c.558C>T) pathogenic?

PGAM2 p.His186= (c.558C>T) is classified Likely benign in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-18). Very rare (popmax 0.00897%, eas); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.His186= (c.558C>T)?

PGAM2 p.His186= (c.558C>T) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.His186= (c.558C>T) in the general population?

PGAM2 p.His186= (c.558C>T) is very rare (popmax 0.00897%, eas) (gnomAD).

PGAM2 p.His186=

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.558C>T · rs371937909 · VCV2042946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00897%, eas)

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -10	GERP -3.7
Overall
CADD	0.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00897% East Asian · 2/22,304 alleles

Filtering AF 0.00217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.00248% 34/1,369,724 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00897%	11,152
Remaining individualsnot grpmax-eligible	0.00641%	15,601
South Asian	0.00572%	17,497
European (non-Finnish)	0.00234%	42,779

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.His186=
Coding: c.558C>T
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs371937909
Type: single nucleotide variant
Location: chr7:44064869 (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-his186 (accessed [today's date]).

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