GAA p.Ala284=
c.852G>A · rs142626724 · VCV188477
ClinGen expert panel — Lysosomal Diseases VCEP
Benign for glycogen storage disease II. Applied ACMG criteria (verbatim):
BA1
Curation rationale (ClinGen, verbatim)
The highest continental population minor allele frequency for c.852G>A (p.Ala284=) in gnomAD v2.1.1 is 0.01017 in the European non-Finnish population. This is higher than the ClinGen LSD VCEP’s BA1 threshold (>0.01), meeting this criterion. There is a ClinVar entry for this variant (Variation ID: 188477, two star review status), with 5 submitters classifying the variant as benign. 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 LSD VCEP: BA1.
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 -3.3 | GERP -3.2 |
| Overall | ||
| CADD | 6.162 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.17% | 46 |
| European (non-Finnish) | 0.974% | 103 |
| Amishnot grpmax-eligible | 0.92% | 109 |
| Remaining individualsnot grpmax-eligible | 0.83% | 120 |
| Ashkenazi Jewishnot grpmax-eligible | 0.727% | 138 |
| Admixed American | 0.519% | 193 |
| Finnishnot grpmax-eligible | 0.301% | 332 |
| South Asian | 0.235% | 426 |
| African / African-American | 0.168% | 594 |
| East Asian | 0.00224% | 44,596 |
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.Ala284=
- Coding
- c.852G>A
- MANE Select
- NM_000152
- dbSNP
- rs142626724
- Type
- single nucleotide variant
- Location
- chr17:80107716 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.32 · 19 PDB
Disease context
glycogen storage disease II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 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.Ala284Gly Uncertain significance ★★ ⚠ same residue
- GAA p.Ala284Val Uncertain significance ★★ ⚠ same residue
- GAA p.Ala284Glu Uncertain significance ★ ⚠ 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
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-ala284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown