Single nucleotide variants represent the most common type of polymorphism in the human genome. However, the phenotypic impacts of these mutations are not well understood in many cases. Intriguingly, while some SNVs cause debilitating diseases, other variants in the same protein may have no or limited effect. The mechanisms underlying these complex interactions are difficult to study at a high throughput scale. In this review we discuss base editing technologies and their potential to accelerate progress in this field, particularly in combination with single-cell RNA sequencing. We then highlight several studies that take advantage of single-cell RNA sequencing and CRISPR screens to emphasize the current limitations and future potential of this technique.