This variant may occur at a frequency greater than expected due to GT. The overall allele frequency on gnomAD v2.1.1 is 0.0005659 with a MAF of 0.001411 (50/35,430 alleles) for the Latino population, below the BS1 threshold. In gnomAD v3 there are 45/13,658 alleles (0.003295) present in the Latino population, above the BA1 threshold. Assuming non-overlapping datasets this is a total of 95/49,088 alleles with a MAF of 0.001935, meeting the 0.00158-0.0024 range for BS1. The more conservative criteria of BS1, rather than BA1, was applied. An "Other" population in gnomAD v2.1.1 has an allele frequency of 0.00194, within the BS1 range, however an undefined population group is not considered.

Computational evidence suggests that there is no impact on the gene with a REVEL score of 0.13, below the threshold of <0.25.

This variant has been observed in cis with the VCEP-curated pathogenic variant Val982Met (PMID 15099289 and 20020534). In an additional proband (PMID 25539746), this variant has also been reported in combination with Val982Met and Glu538Ter, however, the phase of the variants was not confirmed.

Transient expression of the Ala989Thr variant in COS-7 cells and αIIbβ3 cell surface expression detection by flow cytometry demonstrated that the variant does not lead to reduced αIIbβ3 expression levels (expression is ~120% of control expression levels) (PMID 15099289). However, additional studies of the effect of the variant on protein function were not reported and, as a result, this evidence does qualify for BS3.

Internal laboratory data has identified this variant in a 9 yo patient with normal platelet count and no history of bleeding. No aggregation information was provided and it is not known if it was found in a heterozygous or homozygous state. This criteria requires >1 homozygote to be identified so it has not been met.