The PM1 criterion, which states that a variant is located in a mutational hot spot and/or critical and well-established functional domain without benign variation, is considered moderate evidence for assessing its pathogenicity. The application of PM1 criterion is limited due to the lack of a comprehensive and reliable database of variant hotspot regions. Compared to hotspots, coldspots have been neglected by the ACMG guidelines. In order to improve variant classification, we suggest including coldspots in the ACMG guidelines that support the classification of benignity. Consequently, we have developed the HCSeer tool to provide data support for PM1 and the ‘Benign’ criteria. HCSeer employs the Kernel Density Estimation (KDE) algorithm and the Expectation-Maximization (EM) algorithm to identify potential hotspot and coldspot regions. Through our HCSeer, we successfully identified 423 hotspots and 3,942 coldspots regions in 1,523 genes. We then provided a database for general geneticists and clinicians to easily query whether a variant is located in a hotspot or coldspot region ( http://www.genemed.tech/hcseer/ ), so as to determine if it can apply the PM1 of ACMG or the Benign criteria. Availability: Code and Supplementary data are available at https://github.com/xq-xia/HCSeer .