Is GAA p.Asp243fs (c.727_728insCCACCAGGACA) pathogenic?

GAA p.Asp243fs (c.727728insCCACCAGGACA) is classified Pathogenic in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-23). No gnomAD frequency available for this variant; Associated with glycogen storage disease II.

What condition is associated with GAA p.Asp243fs (c.727_728insCCACCAGGACA)?

GAA p.Asp243fs (c.727_728insCCACCAGGACA) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Asp243fs (c.727_728insCCACCAGGACA) in the general population?

GAA p.Asp243fs (c.727_728insCCACCAGGACA) is no gnomAD frequency available for this variant (gnomAD).

GAA p.Asp243fs

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.727_728insCCACCAGGACA · rs2510357510 · VCV2858506

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

glycogen storage disease II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GAA
Protein: p.Asp243fs
Coding: c.727_728insCCACCAGGACA
MANE Select: NM_000152
dbSNP: rs2510357510
Type: Insertion
Location: chr17:80107591 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB

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.Asp243Glu Likely pathogenic ★ ⚠ same residue
GAA p.Asp243= Likely benign ★ same residue
GAA p.Lys114fs Pathogenic ★★★ same condition
GAA c.858+7_858+8insAGCGGGC Benign ★★★ same condition
GAA p.Phe297fs Pathogenic/Likely pathogenic ★★ same condition
GAA c.858+7_858+8insAGCAGGC Benign/Likely benign ★★ same condition
GAA c.858+7_858+8insAGCGGGCGGCGGGC Likely benign ★★ same condition
GAA p.Asn882fs Likely 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-asp243fs (accessed [today's date]).

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