Running a single query of SORVA

How many individuals have a rare variant anywhere in a given gene?

To answer this question, please fill out the form below with the variant filtering thresholds that apply to your study.

Example: studying an autosomal dominant Mendelian disorder

Let's say several of your cases carry rare missense variants in the gene UBC, and you would like to find out if this is significant, given the frequency of variants in the general population. If you had filtered out all variants with a minor allele frequency > 1% before coming to this result, then you can indicate with your selections that you are considering LOF or missense variants, in ALL populations, with MAF <= 0.01, in Binary mode (even if an individual has multiple variants in the gene, count them once), and considering Both homozygous and heterozygous variants. You will be provided the option to calculate the significance of seeing a certain number of variants in the given gene in the following step.

Note: If you've identified heterozygous variants in a gene and would like to to calculate the significance of your findings, you will need to set zygosity to "Both", not to "HeteroOnly".

Another note: Loss-of-function (LOF) variants include all potential LOF variants such as splice-site variants, stop codon gain (nonsense) variants, and frameshift indels.

Analysis thresholds

Protein consequence:	LOF or missense LOF only	How stringent is your filtering according to protein consequence? LOF or missense: considering loss-of-function (LOF) or missense (i.e. nonsynonymous) variants. LOF only: considering potential LOF variants only, which includes splice site mutations, protein truncating stop codon gain mutations, and frameshift indels.
Population:	ALL EAS EUR AFR AMR SAS	Population of interest AFR: African. AMR: Ad Mixed American. EAS: East Asian. EUR: European. SAS: South Asian. ALL: All superpopulations. Detailed descriptions can be found on the 1000 Genomes Project website.
MAF:	0.05 0.01 0.005 0.001 0.0005	Minor allele frequency (MAF) threshold What MAF threshold did you use when filtering variants in your study? Choices correspond to MAF <= 5%, 1%, 0.5%, 0.1% and 0.05%, respectively. If you're unsure of this value, select your threshold based on disease incidence. (Highly penetrant causal variants for rare Mendelian diseases cannot have a high MAF in the population.)
Binarity:	Binary CountVariants	Binarity model If an individual has more than one mutation within a gene, should we count the individual multiple times? Binary: no, count each individual at most one time. This should be the default selection if you're answering the question of how many individuals have a mutation anywhere in the gene? CountVariants: yes, count indivduals multiple times if they have multiple variants in the gene.
Zygosity:	HeteroOnly HomoOnly Both HomOrCompoundHet	Based on your disease inheritance model, what is the zygosity of variants you are considering? HeteroOnly: only count heterozygous variants. HomoOnly: only count homozygous variants. Both: Count heterozygous and homozygous variants. This should be your default selection if you are studying at an autosomal dominant or X-linked disorder. HomOrCompoundHet: Count individuals who are either homozygous for a variant or carry at least two heterozygous variants in the same gene. This should be your default selection if you are studying at an autosomal recessive disorder.
Gene:		Official gene symbol or Ensembl gene ID. E.g. CCDC66 or ENSG00000198947