Dr. Pagon had over 35 years of clinical activity (1975 to 2010) at Seattle Children's Hospital, University of Washington Medical Center, and regional clinics in the states of Washington and Alaska. Her clinical interests were syndrome identification, inherited eye disorders, and disorders of sex differentiation.

In 1996 Dr. Pagon founded GeneReviews (www.genereviews.org), an NIH-funded, peer-reviewed point-of-care resource for clinicians that provides current, clinically relevant, medically actionable information on inherited conditions. From 1996 to 2017 Dr. Pagon served as Editor in Chief and PI of the NIH grants and contracts that support GeneReviews. She currently serves as a Senior Editor.

In 1992 she founded the GeneTests Laboratory Directory, serving as PI of the NIH grants and contracts that supported it until funding ceased in 2013.

She served of the Board of Directors, American Board of Medical Genetics (1998-2003); Board of Scientific Counselors, National Human Genome Research Institute (NHGRI), National Institutes of Health (2000-2004); and Board of Directors, American Society of Human Genetics (2005-2007).

Awards include the American Society of Human Genetics 2006 Award for Excellence in Genetics Education and the 2009 March of Dimes Colonel Harland Sanders Life Time Achievement Award in Medical Genetics, awarded by the American College of Medical Genetics and Genomics.