ClinVar

Description

Variant summary: GAA c.1285C>G (p.Gln429Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 233994 control chromosomes, predominantly at a frequency of 0.0079 within the South Asian subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.1285C>G in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign (3x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as benign.