Is GAA p.Arg594= (c.1782C>A) pathogenic?

GAA p.Arg594= (c.1782C>A) is classified Likely benign in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-24). Absent from gnomAD v4.1; Associated with glycogen storage disease II.

What condition is associated with GAA p.Arg594= (c.1782C>A)?

GAA p.Arg594= (c.1782C>A) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Arg594= (c.1782C>A) in the general population?

GAA p.Arg594= (c.1782C>A) is absent from gnomAD v4.1 (gnomAD).

GAA p.Arg594=

Q: How is Glycogen storage disease due to acid maltase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1782C>A · rs2510381323 · VCV2698375

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glycogen storage disease II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -2.8
Overall
CADD	0.563	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GAA
Protein: p.Arg594=
Coding: c.1782C>A
MANE Select: NM_000152
dbSNP: rs2510381323
Type: single nucleotide variant
Location: chr17:80112605 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 594: a UniProt-annotated variant site (in iopd); a UniProt-annotated variant site (in iopd and lopd)

Full GAA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to acid maltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GAA p.Arg594His Pathogenic ★★★ same residue
GAA p.Arg594Pro Likely pathogenic ★★★ same residue
GAA p.Arg594Cys Uncertain significance ★★★ ⚠ same residue
GAA p.Arg594Ser Likely pathogenic ★ same residue
GAA c.1076-1G>C Pathogenic ★★★ same condition
GAA c.1076-22T>G Pathogenic ★★★ same condition
GAA c.1194+5G>A Likely pathogenic ★★★ same condition
GAA c.1326+1G>A Pathogenic ★★★ 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/gaa-p-arg594 (accessed [today's date]).

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