Expanding African contributions to ClinVar through genetic counselor-led variant curation.

Global variant databases such as ClinVar are vital in linking genetic variation to clinical significance and enabling shared interpretation across laboratories. However, African genetic variants remain underrepresented, comprising under 2% of global ClinVar submissions. This gap reflects inequities in access to genome sequencing, workforce capacity, and data-sharing systems, which limit visibility, contextual interpretation, and re-evaluation of African genetic variation. We describe our experiences of genetic counselor-led variant curation, ClinVar submissions, and ongoing monitoring of germline genetic variants identified in African neuromuscular and amyotrophic lateral sclerosis research cohorts. Between March 2023 and August 2025, the Clinical Omics and Informatics Unit (University of Cape Town) submitted 93 DNA sequence variants to ClinVar spanning 58 genes, including 27 first-time submissions to the database. ClinVar submissions require valid Monarch Disease Ontology (Mondo) identifiers; gaps or inaccuracies were identified (n = 3) and updated, or Mondo disease entities were created to ensure gene-disease pairs were correctly represented. Using African Genome Variation Database frequencies to guide variant classification provided sub-regional context, highlighting population differences and refining interpretations. Furthermore, we maintained a structured follow-up of variant records using ClinVar's "follow" feature. This enabled passive monitoring of new submissions or classification changes, which were evaluated to assess whether reinterpretation or resolution of variants of uncertain significance or those with conflicting assertions were warranted. This work highlights the critical role that African genetic counselors can play as contributors to variant curation in an underrepresented geography, given their expertise in human genetics and clinical reasoning. By embedding African-specific frequency data and locally trained expertise into variant curation pipelines, a sustainable, equity-driven model for genomic knowledge production in Africa is developed. African-led ClinVar contributions can strengthen interpretative accuracy, foster collaborative curation, and position genetic counselors as active agents in global genomic data sharing and interpretation.