FGFR2 encodes a receptor tyrosine kinase in the fibroblast growth factor receptor family that binds fibroblast growth factors and activates signaling pathways (including PI3K/AKT and MAPK) that promote cell growth, division, and differentiation. Germline mutations in FGFR2 cause several inherited craniosynostosis syndromes — including Apert, Crouzon, Pfeiffer, Jackson-Weiss, Beare-Stevenson, and Saethre-Chotzen syndromes — in which the bones of the skull fuse prematurely. FGFR2 also plays an oncogenic role in cancer: somatic mutations, fusions, and amplifications of the gene have been found in endometrial, gastric, and breast cancers and ameloblastomas, and FGFR inhibitors are used as cancer therapies.

FGFR2 germline missense variants cause autosomal dominant craniosynostosis syndromes (Apert, Crouzon, Pfeiffer) through activating effects, and p.Glu116Lys falls in the extracellular ligand-binding region where such variants act. Because no established pathogenic record exists and the evidence is conflicting - ultra-rare population frequency but uniformly benign computational predictions - this variant remains a VUS, neither demonstrated to cause FGFR2-related disease nor shown to be benign.