Screening synthetic nucleic acid orders for sequences of concern is a necessary part of a healthy biosecurity regime, but it exacts costs for nucleic acid providers. Taxonomy is and will remain a critical part of the decision-making process for screening, especially for viral sequences. But, moving forward, the function of a sequence will also be determinative of its level of concern, or lack thereof. Stakeholders continue to debate which functions are “of concern.” However these are ultimately adjudicated, nonviral sequences with unknown or hypothetical functions which, by definition, can bear no resemblance to sequences with concerning functions, must be considered innocent of harmful effects. To qualify as a nonviral sequence of concern, the sequence to which it is the best match must be demonstrated in the published literature to have a function of concern.