GERP++ score¶
GERP++ is a conservation score for a DNA position. It compares the number of changes observed at that position across species with the number expected under a neutral model of evolution. A positive score means fewer changes were observed than expected, which is evidence of evolutionary constraint. A change at a highly conserved position can be more concerning and deserves closer review. GERP++ still scores the position, not the specific alternate DNA letter, so it cannot show on its own that a change is harmful or causes disease.
Score range in Gene Inspector Pro¶
GERP++ does not have one fixed numeric range. The possible values depend on the genome build, multiple-species alignment, phylogenetic tree, neutral-rate model, and annotation release. Gene Inspector Pro maps the value to a visual range for display and uses these review bands:
| Score | Display meaning |
|---|---|
| 0 or lower | Less conserved or faster-evolving position |
| Above 0 to 2 | Some evidence of evolutionary conservation |
| Above 2 | Conserved position |
These are display bands, not clinical thresholds. A conserved position may be biologically important, but conservation alone does not show what a particular DNA change does.
Limits of conservation scores¶
Different substitutions at the same position can have very different effects even though they share a GERP++ score. Scores can be missing when the alignment is shallow or gapped. Conservation may also miss recently evolved or lineage-specific human functions.
How to use it¶
Use GERP++ as context for other evidence. Check the affected transcript and consequence, population frequency, ClinVar submissions, functional evidence, inheritance, and genotype quality. Do not treat a high positive score as proof of pathogenicity or a negative score as proof of benignity.