ABSTRACT Syndromic disorders account for a large proportion of the rare genetic disorders that impact the pediatric population, including many conditions with structural birth defects and other congenital anomalies. These conditions are a disproportionate cause of morbidity and mortality. Accurate molecular diagnosis is important for medical management, family planning, and engagement in research studies. Next generation sequencing has driven the pace of discovery of novel genetic syndromes, yet there are marked inconsistencies in the level of evidence for gene-disease relationships (GDRs) that complicate the application of genetic testing. We have formed the Syndromic Disorders Gene Curation Expert Panel (SD-GCEP), an international group of disease experts, gene curation framework experts, and biocurators representing 23 institutions across 5 continents to thoroughly curate the evidence supporting the relationship of a gene in causing a disease, and to quantify the strength of that evidence using the framework developed by the Clinical Genome Resource (ClinGen). The SD- GCEP consists of representatives from major stakeholders including Online Mendelian Inheritance in Man (OMIM), Monarch Initiative’s Mondo disease ontology, Genomics England PanelApp, PanelApp Australia, Centers for Mendelian Genomics, diagnostic laboratories (Ambry, Illumina, Invitae), practicing clinical geneticists, genetic counselors, and rare disease and model organism researchers. In Aim 1, we will perform 68 GDR precurations, curations and recurations representing the most commonly tested syndromic disorders not within the purview of other GCEPs, which generally focus on a specific organ or pathway. In Aim 2, we will perform 89 precurations, curations, and recurations for syndromic GDRs identified through clinical exome and genome sequencing performed by diagnostic laboratories with personnel involved in the SD-GCEP. In Aim 3A, we will perform 24 precurations, curations, and recurations for newly discovered syndromic GDRs from the Centers for Mendelian Genomics, as these are of high interest to diagnostic laboratories to determine when genes should be added to panels and to clinicians to guide clinical diagnosis and management. The SD-GCEP is highly experienced and collaborative. In Aim 3B, we will continue to accept requests from other GCEPs to curate 15 GDRs of interest that are beyond the scope of the other GCEP due to the syndromic nature of the condition. In total, we will perform 196 precurations, curations, and recurations of GDRs for syndromic disorders over three years. All curations will be performed using the ClinGen Gene Curation Interface and publicly shared though the ClinGen knowledgebase to improve genetic testing and diagnosis for syndromic disorders and to highlight where further research is needed.