ERBB2 (HER2) is a well-studied oncogene with several driver mutations apart from the well-known amplification defect in some breast cancers. There is a general lack of uniformity in assessment and relative impact of each variant on the receptor tyrosine kinase function of the protein product. Herein, we evaluated their relative oncogenic potential by HER2 phosphorylation in a low-throughput flow cytometry assay and in the GigaAssay. The GigaAssay is a modular high-throughput one-pot assay system for simultaneously measuring molecular function of thousands of genetic variants at with high accuracy. These two experiments had very high concordance with benchmark mutations and were a major advancement when compared to other variant classification approaches.