What is Fabry predictor?

Fabry predictor is a tool to predict the functional significance of missense variants of GLA from the Clinical and Translational Bioinformatics research group at Vall d'Hebron Institute of Research.

How can I analyze my variant?

You can submit your variant in our query page indicating the native amino acid, the residue and the mutated amino acid. Afterwards, you will be redirect to the prediction page.

Why is my variant not accepted?

We map your variant to the canonical isoform of the protein provided by UniProt (UniProt Consortium, 2023). If the native amino acid of your variant does not match the native amino acid in the canonical isoform, the program will raise an error message. This may happen if your sequence is based on another isoform of UniProt, NCBI or Ensembl.

What information we provide for a pathogenicity prediction?

We provide:

  • Label: the variant is classified as pathogenic or neutral according to its functional consequence.

  • Score: the numerical score of the functional consequence of the variant. It has a continuous scale from 0 to 1, being 0 a neutral and 1 a pathogenic variant. The threshold between pathogenic and neutral variant is at 0.5.

  • Reliability: measures the accuracy of the prediction. It has a continuous scale from 0 to 1, being 1 a truthful prediction.

Score Plot

How are the pathogenicity predictions calculated?

These predictions are calculated by a machine learning algorithm previously trained with a set of already known variants from the literature. To develop the predictor, we followed these steps:

  1. Collect the pathogenic and neutral variants of the protein

  2. Decipher the features able to discriminate between pathogenic and neutral variants

  3. Build the model by training the machine learning algorithm with the set of features of the known variants

  4. Estimate the model performance by cross-validation to ensure the reliability of the predictor

Predictor schema

Riera et alt., Human Mutation, 2016

What is the performance of Fabry predictor?

The Fabry predictor has been evaluated and compared to the state of the art predictors. Compare the performance metrics per predictor:

Sensitivity Specificity Accuracy MCC Coverage
Fabry 0.89 0.911 0.893 0.647 100%
PON-P2 0.954 1.0 0.961 0.866 52%
PolyPhen-2 0.927 0.839 0.917 0.675 100%
CADD 0.934 0.844 0.925 0.669 31%

Can I download all the predictions for my protein?

Yes, you can download all the pre-calculated predictions here. The file is in csv format and has the following columns:

# Field Description
1 Gene HGNC official gene symbol
2 Protein Uniprot accession number
3 Variant Missense variant from the canonical isoform
4 Prediction Predicted functional consequence of the variant
5 Score Numerical score of the pathogenic prediction

Is there any additional information provided with the pathogenicity prediction?

The results report a great amount of information related to the variant divided in different sections: