---
title: Improved ACMG rule PM1
description: Rule PM1 now only considers missense & in-frame variants when evaluating a hot-spot.
---

[VarSome - Platform Updates](https://updates.varsome.com/en)

# [Improved ACMG rule PM1](https://updates.varsome.com/en/improved-acmg-rule-pm1)

 Written by [Richard Meyer](https://updates.varsome.com/en/author/richard-meyer) | Nov 6, 2020, 3:42:13 PM

Rule PM1 now only considers missense & in-frame variants when evaluating a hot-spot. This significantly reduces false-positives, though it does have a small impact on sensitivity too.

For example: variant [BRCA1:Lys503Arg](https://varsome.com/variant/hg19/BRCA1%3ALys503Arg) would previously trigger PM1, when in fact there are no pathogenic missense variants in this area, although there are many null variants:

If we filter the above for missense variants we obtain:

With thanks to Roberto Doliana Ph.D, National Cancer Institute, CRO-IRCCS, Italy, for bringing this issue to our attention.

**Check out the complete VarSome's ACMG documentation for more details:**

- [https://varsome.com/about/resources/acmg-implementation/](https://varsome.com/about/resources/acmg-implementation/)

[View full post](https://updates.varsome.com/en/improved-acmg-rule-pm1)

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