GAA p.Pro444=
c.1332T>C · rs200007324 · VCV286018
ClinGen expert panel — Lysosomal Diseases VCEP
Likely Benign for glycogen storage disease II. Applied ACMG criteria (verbatim):
BS1 BP7 BP4
Curation rationale (ClinGen, verbatim)
The NM_000152.5:c.1332T>C (p.Pro444=) variant in GAA is a synonymous (silent) variant that is not predicted to impact splicing; the nucleotide is not highly conserved (PhyloP 100 way score is -2.4 (BP4, BP7). There is a ClinVar entry for this variant (Variation ID: 286018). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BS1, BP4, BP7. (Classification approved by the ClinGen Lysosomal Diseases VCEP, March 13, 2023).
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 -11 | GERP -2.9 |
| Overall | ||
| CADD | 1.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.09% | 92 |
| South Asian | 0.119% | 843 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,904 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00333% | 30,001 |
| European (non-Finnish) | 0.000254% | 393,212 |
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.Pro444=
- Coding
- c.1332T>C
- MANE Select
- NM_000152
- dbSNP
- rs200007324
- Type
- single nucleotide variant
- Location
- chr17:80109950 (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.Pro444Arg 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-pro444 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown