Summary: A deleteriousness prediction score for missense variants based on regional missense constraint. The range of MPC score is 0 to 5. The larger the score, the more likely the variant is pathogenic. Given increasing numbers of patients who are undergoing exome or genome sequencing, it is critical to establish tools and methods to interpret the impact of genetic variation. While the ability to predict deleteriousness for any given variant is limited, missense variants remain a particularly challenging class of variation to interpret, since they can have drastically different effects depending on both the precise location and specific amino acid substitution of the variant. In order to better evaluate missense variation, we leveraged the exome sequencing data of 60,706 individuals from the Exome Aggregation Consortium (ExAC) dataset to identify sub-genic regions that are depleted of missense variation. We further used this depletion as part of a novel missense deleteriousness metric named MPC. We applied MPC to de novo missense variants and identified a category of de novo missense variants with the same impact on neurodevelopmental disorders as truncating mutations in intolerant genes, supporting the value of incorporating regional missense constraint in variant interpretation. Details see doi:


tabix -s 1 -b 2 -e 2 -f fordistconstraintofficialmpcvalues_v2.txt.gz

  • reference_genome: hg19/genomes/GATK_ResourceBundle_5777_b37_phiX174


id type default annotation description histogram range
MPC float


Missense badness, PolyPhen-2, and Constraint. A deleteriousness prediction score for missense variants" HISTOGRAM FOR MPC [0.000, 5.000]


Filename Size md5
fordist_constraint_official_mpc_values_v2.txt.gz 2.26 GB a208ddc5f6b1d95afd9f76ac6b22f9c4
fordist_constraint_official_mpc_values_v2.txt.gz.dvc 122.0 B e28025a0023c85887370fa20921d9285
fordist_constraint_official_mpc_values_v2.txt.gz.sha 230.0 B ad7119f38b88bc99fd24cdd1dd045bd1
fordist_constraint_official_mpc_values_v2.txt.gz.tbi 723.86 KB 877cb8feebc49c22b6956928fb77f5b8
fordist_constraint_official_mpc_values_v2.txt.gz.tbi.dvc 122.0 B 56d2aaf0fa5c2e323eee468bd16cc62d
genomic_resource.yaml 2.31 KB 55a41e0269abc6cc4caad826fc05562a