RUO

Research Use Only (RUO) is a regulatory designation for products intended for research applications, not for use in clinical diagnosis or treatment decisions. RUO products are not FDA-cleared or approved as diagnostic devices.

What It Means in Practice

An RUO designation means:

• The tool provides computational evidence to support research
• Clinical laboratories may use RUO scores within their own validated workflows (as part of a laboratory-developed test, or LDT)
• The responsibility for clinical validation lies with the laboratory, not the tool developer

Precedent: Established Computational Variant Predictors

Major computational variant effect predictors are all RUO:

Tool	RUO	ACMG Evidence Code
REVEL	Yes	PP3/BP4
CADD	Yes	PP3/BP4
AlphaMissense	Yes	PP3/BP4
PolyPhen-2	Yes	PP3/BP4
SIFT	Yes	BP4
ESM-2 (NeuroAutomata)	Yes	PP3/BP4

These tools contribute ACMG evidence criteria PP3 (computational evidence pathogenic) and BP4 (computational evidence benign) when incorporated into a clinical variant classification workflow.

RUO Is Not a Limitation

RUO does not mean the tool is unvalidated or unreliable. It means the tool is positioned appropriately within the clinical evidence hierarchy. The DMS validation benchmarks in the ESM-2 Benchmark Series document exactly where and how well the scores perform — which is what clinical labs need to assess before incorporating any computational tool.