Is PGAM2 p.Arg141Gln (c.422G>A) pathogenic?

PGAM2 p.Arg141Gln (c.422G>A) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: ambiguous (0.4801); Ultra-rare (popmax 0.0165%, mid); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Arg141Gln (c.422G>A)?

PGAM2 p.Arg141Gln (c.422G>A) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Arg141Gln (c.422G>A) in the general population?

PGAM2 p.Arg141Gln (c.422G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PGAM2 p.Arg141Gln (c.422G>A)?

AlphaMissense predicts ambiguous (score 0.4801) — an in-silico prediction, not a clinical call.

PGAM2 p.Arg141Gln

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.422G>A · rs144310510 · VCV2194940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.4801	ambiguous
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -12.99	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	29.6	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00168% 27/1,606,222 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.00666%	15,007
Admixed American	0.00334%	29,918
Remaining individualsnot grpmax-eligible	0.0016%	62,416
European (non-Finnish)	0.00153%	65,528

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.Arg141Gln
Coding: c.422G>A
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs144310510
Type: single nucleotide variant
Location: chr7:44065005 (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-arg141gln (accessed [today's date]).

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