This study aimed to obtain a quantitative assessment of the occurrence of contradictory evidence in functional classification of genetic variation, according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We analyzed 140,883 genetic variation in the Human Gene Mutation Database (HGMD). The 2014 release of the HGMD dataset before the publication of the ACMG guidelines was used for its independence from the ACMG guidelines. Evidence for benign classification, BS2 (0.37%), was identified among variants classified as pathogenic. For likely pathogenic variation, BP1 (2.99%) and BS2 (0.37%) were identified. PM1 is commonly observed among variants classified as benign (28.45%), while PM2 and PM1 are commonly identified among variants classified as likely benign (48.91% and 42.95%, respectively). Taken together, these observations will inform better approaches to apply the ACMG guidelines.