{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:36Z","timestamp":1791385056711,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Variant databases ClinVar and gnomAD underpin clinical variant interpretation, but their composition is skewed toward European ancestry. Whether this produces systematic disadvantages for non\u2010European patients with monogenic diabetes has not been examined at the database level with mutually exclusive ancestry groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify ClinVar annotation coverage and ancestry\u2010stratified classification outcomes across monogenic diabetes genes, using mutually exclusive population\u2010private variant groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>gnomAD v4.0 (genomes and exomes; 807,162 individuals) was cross\u2010referenced with the ClinVar GRCh38 record (accessed June 29, 2026) for 16 monogenic diabetes (maturity\u2010onset diabetes of the young [MODY]) genes, and variants were classified as population\u2010private to European or non\u2010European ancestry from ancestry\u2010specific allele counts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across 54,865 gnomAD variants, 86.7% carried no ClinVar classification. The annotation gap was near\u2010universal rather than ancestry\u2010specific (unannotated fraction 89.4% European\u2010private, 87.5% non\u2010European\u2010private). Among classified population\u2010private variants, however, the pathogenic or likely pathogenic rate was 19.8% for European\u2010private but only 8.6% for non\u2010European\u2010private variants (Fisher exact OR 2.6, 95% CI 2.1\u20133.3,\n                      <jats:italic>p<\/jats:italic>\n                      = 1 \u00d7 10\n                      <jats:sup>\u2212<\/jats:sup>\n                      <jats:sup>1<\/jats:sup>\n                      <jats:sup>8<\/jats:sup>\n                      ), with a higher uncertain\u2010significance rate in non\u2010European\u2010private variants (52.1% vs. 45.8%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The dominant problem is therefore an annotation deficit affecting all ancestries; the ancestry inequity the data support is one of actionability, not of raw uncertain\u2010significance rates. Closing it requires ClinVar submissions and population\u2010specific sequencing from underrepresented populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70054","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:43:20Z","timestamp":1787553800000},"page":"346-355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ancestry\u2010Stratified Variant Classification in Monogenic Diabetes Genes: Annotation Coverage and Differential Curation Burden"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-9179","authenticated-orcid":false,"given":"Paulo","family":"Dario","sequence":"first","affiliation":[{"name":"Departamento da Promo\u00e7\u00e3o da Sa\u00fade e Preven\u00e7\u00e3o de Doen\u00e7as N\u00e3o Transmiss\u00edveis Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge (INSA)  Lisboa Portugal"},{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL), Faculdade de Medicina Universidade de Lisboa  Lisboa Portugal"},{"name":"BioSystems &amp; Integrative Sciences Institute (BioISI), Faculdade de Ci\u00eancias Universidade de Lisboa  Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000539542"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438\u2010025\u201002295\u2010x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592\u2010016\u20100859\u20108"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010024\u201001392\u20107"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592\u2010025\u201002449\u20108"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010130"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2025.101501"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856\u2010025\u201001031\u20101"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001947\u20109"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","unstructured":"Jones S. 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