Resolving unsolved cases in rare genetic and non‑genetic diseases through variant validation and new technological approaches

An information webinar will be held on December 16th, 2025, 15.00-16.00 (CET). Register to participate in the webinar here.

Preliminary Announcement

The content and procedures of the call described in this pre-announcement may be subject to change and are not legally binding.

The aim of the call is to tackle RD (rare disease) patient-need led challenges and enable scientists to build, based on common interests and sharing of expertise, effective, multinational, interdisciplinary research collaborations. The expected impact lies in the future translation and use of the results to the benefit of patients.

The classification of RDs follows the European definition, i.e. a disease affecting not more than five in 10.000 persons in the European Community, EC associated states, and Canada.

Accurately diagnosing RDs is a major challenge, with approximately 50% of individuals with a suspected of having rare genetic condition remaining undiagnosed or misdiagnosed despite standard clinical genetics care. In addition, RDs of non-genetic origin – estimated to account for about 10% of all RD cases – remain an under-investigated area. On average, it takes around 5 years to establish an accurate diagnosis for people living with a RD (PLWRD). Given the complexity of these disorders, multiple and complementary diagnostic approaches are required. These unmet needs and challenges underpin the objectives of this call.

Call Topic

The goal of this call is to solve Undiagnosed Rare Genetic diseases and to address complex, multifactorial Rare Non-Genetic diseases by identifying causative variants in patients with no molecular diagnosis after prior genetic or genomic testing and providing diagnostic clarity for conditions of unknown or mixed pathogenesis.

Suggested focus areas are:

• Functional validation to classify variants of uncertain significance (VUS) and increase the diversity of functional genomics research, or validation of candidate VUS to improve outcomes for a broader range of patients using in silico, in vitro or animal model systems (e.g. CRISPR modified cells, iPSCs, organoids, etc.);
• Use of multi-omics or integrative methods (e.g. transcriptomics, epigenomics, etc.) to resolve ambiguous or complex variants;
• New tools/methodologies not yet validated in clinical settings, including biostatistics, advanced bioinformatics, and mathematics approaches (e.g. variant effect predictors, Artificial Intelligence (AI)-based annotation platforms, etc.);
• Systems biology and disease mechanism modelling;
• Integration of clinical, environmental, lifestyle, and sensor-derived data;
• Development of knowledge graphs or disease maps to link phenotypic and mechanistic insights;
• Use of advanced AI and modelling tools (graph ML, probabilistic causal models).

SME or industry/large enterprise partners are funded with up to 50% of their eligible project costs. See Conditions for awarding state aid for more details. 

Website: https://erdera.org/call/joint-transnational-call-2026/