Recent articles in JMG exemplify a broader shift from cataloguing gene-disease associations to estimating clinically calibrated variant effects. Large sequencing cohorts are coupled with deep clinical characterisation to (1) delineate how inherited variants contribute to adult disease risk (https://jmg.bmj.com/content/early/2026/02/10/jmg-2025-111201), (2) expand and refine genotype-phenotype relationships for rare neurodevelopmental and syndromic conditions (https://jmg.bmj.com/content/early/2026/01/29/jmg-2025-111027; https://jmg.bmj.com/content/early/2026/01/28/jmg-2025-111040), and (3) reassess penetrance, including possible null effects, for proposed cancer and cardiovascular risk alleles (https://jmg.bmj.com/content/early/2026/01/29/jmg-2025-111119 ). (See more at: https://jmg.bmj.com/content/early/recent )