---
title: How do the Phenogenius scoring and HPO filtering work?
description: Learn how PhenoGenius calculates gene-HPO association scores, and the difference between Recommended and Union filtering modes.
---
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# How do the Phenogenius scoring and HPO filtering work?
## Learn how PhenoGenius calculates gene-HPO association scores, and the difference between Recommended and Union filtering modes.
The HPO Phenotypes filter operates to filters genes based on the strength of the association between a patient's clinical features (phenotypes) and known disease genes. This process relies entirely on the calculated **PhenoGenius score**.
### 1. PhenoGenius Score Calculation
The final PhenoGenius score for any given gene reflects the aggregated evidence linking that gene to the patient's entire set of HPO terms.
- Scoring a Single HPO Term : For each HPO term provided by the user, the system retrieves a **gene-HPO association score** (ranging from 0% to 100% on the platform). This score is computed from a set of **curated sources** (e.g., OMIM, MedGen, hpo.jax, LitVar, PanelApp, EBI, Orphanet, and Monarch).
In the platform, you can view the gene–HPO association score by opening the Phenogenius pop-up window after clicking on numbers displayed in the Phenotypes column.
- Scoring for multiple HPO terms : When a patient has a set of multiple HPO terms describing their phenotype, PhenoGenius computes a single, **multi-HPO phenotype-gene** **association** score for each gene. This score is calculated by **averaging all the gene-HPO association scores**. This average score is what is used in the DiagAI score computation.
⚠️ Warning: This means that adding unrelated or uncertain HPO terms "to test the system" will influence the ranking, as it affects the overall average score.
💡 The global gene ranking—compared with all other genes and based on the mean score of all provided HPOs—is displayed in the Phenogenius pop-up window. You can sort the entire Variant Table by this ranking using the sort mode "Phenotype".
### 2. The Filter Mechanism
The HPO gene filter uses the calculated PhenoGenius score to determine which genes and variants to suggest to the user. Two filtering modes are offered, each using a different minimum score threshold:
The filter uses the PhenoGenius score to intelligently narrow down the list of candidate genes by requiring strong and consistent association evidence for each clinical symptom. You can download this list directly from the filter by clicking on "**See gene list**".
💡 *Note:* The provided gene list is based on the Phenogenius association scores and on the threshold selected. It will **not match** raw HPO-gene lists from other sources, such as the [Jax-HPO](https://hpo.jax.org/) website. This is designed to provide you with a shorter, more specific list.
### 3. Illustrative Example (Recommended Mode)
Consider the NM\_001191061.2(**SLC25A22**):c.813\_814del variant with the following HPO terms:
If you select both HPO terms in the filtering menu (shown here on **Recommended** settings), the final PhenoGenius score is calculated as:
PhenoGenius Score = (0.65 + 0.42)/2 = 0.535.
- The score 0.535 is **greater than the Recommended mode threshold of 0.106**.
- **Result:** The NM\_001191061.2(**SLC25A22**):c.813\_814del variant is therefore retained in the filtered Variant Table.
👉 Want to dive deeper into the methodology behind PhenoGenius? Read the original publication: [Learning phenotypic patterns in genetic disease by symptom interaction modeling](https://www.medrxiv.org/content/10.1101/2022.07.29.22278181v3).
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