Preeclampsia is a common pregnancy-specific vascular disorder characterized by new-onset hypertension and proteinuria during the second half of pregnancy. The etiology of the disease is unknown but predisposition to preeclampsia is in part heritable. Preeclampsia is associated with an increased risk of cardiovascular disease later in life. We have sequenced 124 candidate genes implicated in preeclampsia to pinpoint genetic variants contributing to predisposition to or protection from preeclampsia. First, targeted exomic sequencing was carried out in 500 preeclamptic women and 190 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Then 122 women with a history of preeclampsia and 1,905 parous women with no such history from the National FINRISK Study were included in the analyses. We tested 146 rare and low-frequency variants and found an excess (observed 13 versus expected 7.3) nominally associated with preeclampsia (p< 0.05). The most significantly associated sequence variants were protective variants rs35832528 (E982A; p=2.49E-4, OR=0.387) and rs141440705 (R54S; p=0.003, OR=0.442) in Fms Related Tyrosine Kinase 1 (FLT1). These variants are enriched in the Finnish population with minor allele frequencies 0.026 and 0.017, respectively. They may also be associated with a lower risk of heart failure in 11,257 FINRISK women. This study provides the first evidence of maternal protective genetic variants in preeclampsia.