Is GAA p.Pro511= (c.1533C>G) pathogenic?

GAA p.Pro511= (c.1533C>G) is classified Likely benign in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-25). Very rare (popmax 0.00223%, eas); Associated with glycogen storage disease II.

What condition is associated with GAA p.Pro511= (c.1533C>G)?

GAA p.Pro511= (c.1533C>G) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Pro511= (c.1533C>G) in the general population?

GAA p.Pro511= (c.1533C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

GAA p.Pro511=

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.1533C>G · rs1598581655 · VCV754496

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 0.063	GERP -2.3, phastCons 0.89
Overall
CADD	7.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 6.2e-05% 1/1,614,128 alleles · very rare exomes 1/1,461,834 · genomes 0/152,294 · joint denominator

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.Pro511=
Coding: c.1533C>G
MANE Select: NM_000152
dbSNP: rs1598581655
Type: single nucleotide variant
Location: chr17:80110822 (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.Pro511Leu Uncertain significance ★★ ⚠ same residue
GAA p.Pro511His Likely pathogenic ★ ⚠ same residue
GAA p.Pro511Thr 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-pro511 (accessed [today's date]).

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