To the Editor: In 2015, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) promulgated recommendations for the interpretation of sequence variants. 1 These recommendations have been widely implemented and shown to be useful for improving variant classification consistency. 2–4 From the beginning, they were recognized to be a starting point for further future refinements and extensions. The Clinical Genome (ClinGen) Resource is focused on curating the genome for use in molecular diagnosis. 5 One such effort is the Sequence Variant Interpretation Working Group, which has taken on the task of refining and evolving the current ACMG/AMP recommendations. This working group meets regularly and also, as individuals, interacts widely with the clinical testing community. Through these interactions, the working group has received input from multiple sources that two related criteria in the original recommendations should be considered for removal from the ACMG/AMP framework: