Here we provide novel convergent evidence across three independent cohorts of healthy adults ( n = 531), demonstrating that a common polymorphism in the gene encoding the α2 subunit of neuronal voltage-gated type II sodium channels ( SCN2A ) predicts human general cognitive ability or “ g .” Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher “ g ” independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort ( n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral PFC and dorsal ACC, which support higher cognitive functions. Collectively, these findings fill a gap in our understanding of the genetics of general cognitive ability and highlight a specific neural mechanism through which a common polymorphism shapes interindividual variation in “ g. ”