Single-nucleotide evolutionary constraint scores highlight disease-causing mutations

Identifying disease-causing genetic variants in individual human genomes is a major challenge, even in protein-coding exons (the `exome'). Analysis of nucleotide-level sequence conservation may help address this challenge, on the assumption that purifying selection `constrains' evolutionary divergence at phenotypically important nucleotides. In contrast to functional classifiers (for example, non-synonymous mutations), constraint scores are...