Is PGAM2 p.Arg86His (c.257G>A) pathogenic?

PGAM2 p.Arg86His (c.257G>A) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: ambiguous (0.5594); Ultra-rare (popmax 0.0916%, amr); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Arg86His (c.257G>A)?

PGAM2 p.Arg86His (c.257G>A) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Arg86His (c.257G>A) in the general population?

PGAM2 p.Arg86His (c.257G>A) is ultra-rare (popmax 0.0916%, amr) (gnomAD).

What do computational predictors say about PGAM2 p.Arg86His (c.257G>A)?

AlphaMissense predicts ambiguous (score 0.5594) — an in-silico prediction, not a clinical call.

PGAM2 p.Arg86His

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.257G>A · rs766643060 · VCV2076137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0916%, amr)

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	0.5594	ambiguous
REVEL	0.573	indeterminate
SaProt	LLR -10.99	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	25.1	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 0.0916% Admixed American · 55/60,012 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0653%

Overall 0.00663% 107/1,613,540 alleles · ultra-rare exomes 93/1,461,290 · genomes 14/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0916%	1,091
East Asian	0.0557%	1,796
Middle Eastern	0.0164%	6,084
African / African-American	0.012%	8,328
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.00329%	30,365
Finnishnot grpmax-eligible	0.00158%	63,452
European (non-Finnish)	0.000508%	196,675

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.Arg86His
Coding: c.257G>A
MANE Select: NM_000290
dbSNP: rs766643060
Type: single nucleotide variant
Location: chr7:44065273 (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-arg86his (accessed [today's date]).

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