Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by a combination of rare de novo and inherited variants as well as common variants in at least several hundred genes. However, significantly larger sample sizes are needed to identify the complete set of genetic risk factors. We conducted a pilot study for SPARK (SPARKForAutism.org) of 457 families with ASD, all consented online. Whole exome sequencing (WES) and genotyping data were generated for each family using DNA from saliva. We identified variants in genes and loci that are clinically recognized causes or significant contributors to ASD in 10.4% of families without previous genetic findings. Additionally, we identified variants that are possibly associated with autism in an additional 3.4% of families. A meta-analysis using the TADA framework at a false discovery rate (FDR) of 0.2 provides statistical support for 34 ASD risk genes with at least one damaging variant identified in SPARK. Nine of these genes (BRSK2, DPP6, EGR3, FEZF2, ITSN1, KDM1B, NR4A2, PAX5 and RALGAPB) are newly emerging genes in autism, of which BRSK2 has the strongest statistical support as a risk gene for autism (TADA q-value = 0.0015). Future studies leveraging the thousands of individuals with ASD that have enrolled in SPARK are likely to further clarify the genetic risk factors associated with ASD as well as allow accelerate autism research that incorporates genetic etiology.