Is GAA p.Ser800= (c.2400C>T) pathogenic?

GAA p.Ser800= (c.2400C>T) is classified Benign in GAA (ClinVar, Expert panel, 12 submitters; last evaluated 2024-08-06). Low-frequency (popmax 2.42%, afr); Associated with glycogen storage disease II.

What condition is associated with GAA p.Ser800= (c.2400C>T)?

GAA p.Ser800= (c.2400C>T) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Ser800= (c.2400C>T) in the general population?

GAA p.Ser800= (c.2400C>T) is low-frequency (popmax 2.42%, afr) (gnomAD).

GAA p.Ser800=

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.2400C>T · rs115705591 · VCV167115

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.42%, afr)

Conditions

glycogen storage disease II

ClinGen expert panel — Lysosomal Diseases VCEP

Benign for glycogen storage disease II. Applied ACMG criteria (verbatim):

BA1

Curation rationale (ClinGen, verbatim)

The NM_000152.5:c.2400C>T variant in GAA is a synonymous (silent) variant (p.Ser800=) that is not predicted to impact splicing. The highest population minor allele frequency in gnomAD v2.1.1. is 0.02504 (617/24640 alleles; 9 homozygotes) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.01), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 167115. In summary, this variant meets the criteria to be classified as Benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (specifications Version 2.0): BA1. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on August 6, 2024).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 -1.2	GERP -2.4
Overall
CADD	7.227	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.42% African / African-American · 1,819/75,038 alleles

Filtering AF 2.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.29%

Overall 0.125% 2,015/1,612,816 alleles · low-frequency exomes 995/1,460,500 · genomes 1,020/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.42%	41
Admixed American	0.148%	674
Remaining individualsnot grpmax-eligible	0.126%	791
Middle Eastern	0.0332%	3,009
European (non-Finnish)	0.0022%	45,383

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: GAA
Protein: p.Ser800=
Coding: c.2400C>T
MANE Select: NM_000152
dbSNP: rs115705591
Type: single nucleotide variant
Location: chr17:80117668 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 800: a β-strand

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.Ser800Ile Conflicting classifications of pathogenicity ★ ⚠ 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
GAA c.1327-2A>G Pathogenic ★★★ same condition
GAA c.1437+1G>A Likely pathogenic ★★★ same condition
GAA c.1437+2T>C 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-ser800 (accessed [today's date]).

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