Suvorova et al. 2026 Carrier Frequencies of Medically Actionable Pathogenic Variants in the Russian Population

Suvorova et al. 2026 analyzed whole-genome sequences from 42,826 unrelated, generally healthy adult volunteers in Russia to estimate the frequency of clinically actionable secondary findings in ACMG SF v3.2 genes.¹

Bibliographic Details

• Citation: Suvorova, Y., Monakhova, A., Chekanov, N., Musharova, O., Moskovkina, E., Zaigrin, I., Antonov, I., Klimchuk, O., Pustoshilov, D., Zorina, D., Klimuk, E., & Severinov, K. (2026). Carrier frequencies of medically actionable pathogenic variants in the Russian population. International Journal of Molecular Sciences, 27, 5344. https://doi.org/10.3390/ijms27125344
• Source type: open-access journal article; pasted PDF text.
• Data source: National Genetic Initiative whole-genome sequences from healthy volunteers across major Russian urban areas.¹

Study Design

• The study screened 42,826 unrelated, generally healthy adult volunteers aged 18-89 years; 61% were female and the median age was 39.¹
• Participants came from urban populations across Moscow, St. Petersburg, Ryazan, Krasnodar region, Samara region, Tyumen region, Krasnoyarsk region, Bashkortostan, Khanty-Mansiysk, and the Udmurt Republic.¹
• Self-reported ethnicity was 60.5% Russian, with Tatars (8.6%), Bashkirs (2%), Ukrainians (1.4%), Udmurts (1.3%), Chuvash (0.92%), Armenians (0.54%), and Mari (0.45%) as the largest named minority groups; approximately 15% could not be assigned because responses were ambiguous.¹
• The analysis focused on known pathogenic and likely pathogenic ClinVar variants in the 81 ACMG SF v3.2 genes associated with treatable or preventable monogenic conditions.¹
• The study also searched for candidate potential loss-of-function variants in dominant ACMG SF genes not listed in ClinVar, excluding genes where loss of function is not a known disease mechanism.¹

Key Findings

• Secondary findings were detected in 1186 of 42,826 participants, giving an overall frequency of 2.76%.¹
• Cancer-associated findings were the most common category, present in 565 participants (1.32%), followed by cardiovascular findings in 454 participants (1.05%).¹
• The most frequent genes among genotype-positive participants were BRCA1 (190 GPPs), BRCA2 (153), RYR1 (108), and LDLR (105).¹
• The most common phenotypes were hereditary breast and ovarian cancer, hypertrophic and dilated cardiomyopathy, familial hypercholesterolemia, malignant hyperthermia susceptibility, and Lynch syndrome.¹
• Heterozygous carrier status for recessive ACMG SF genes was common: 4117 participants (9.6%) carried one pathogenic or likely pathogenic recessive-gene variant.¹
• Candidate pLOF variants in dominant ACMG SF genes were found in 280 participants (0.65%); if confirmed orthogonally, these could raise the secondary-finding frequency from 2.76% to 3.41%.¹
• Questionnaire analysis found that cancer-history reporting was higher among carriers of cancer-category secondary findings than among participants without oncological findings: 8.04% versus 2.30%, with age- and sex-adjusted OR 3.88.¹

Population-Specific Variant Signals

• Several frequent variants had higher frequencies in the Russian NGI cohort than in any gnomAD cohort, suggesting population-specific or underrepresented-ancestry effects in Russian and Slavic populations.¹
• Known Slavic founder variants included BRCA1 rs80357906 and rs80357711 and BRCA2 rs80358754.¹
• Some variants were concentrated in self-identified Tatars and Bashkirs, including LDLR rs377437226, BRCA1 rs28897672, BRCA2 rs758732038, SCN5A rs199473083, MSH6 rs267608055, and RYR1 rs111888148.¹
• BRCA2 rs80359361 was found in nine genotype-positive participants, six of whom self-identified as Udmurts.¹
• A new stop-gained candidate pLOF variant in BRCA2 (c.2521A>T) was found in four participants, all of whom self-identified as Udmurts.¹

Interpretation For Russian Ancestry Context

This paper strengthens the vault’s Russian ancestry genetics context by showing that rare clinically actionable variants can have different frequency patterns across Russian self-identified groups. For the PBMC ancestry project, it supports the general need for Russian-population-aware genetic interpretation, but it is not direct evidence about T2D, PBMCs, or immune-cell phenotypes.²

Limitations

• The cohort was urban and healthy-volunteer based, so frequencies may not generalize to all Russian populations or rural groups.²
• Ethnicity was self-reported; the authors note that genotype-inferred ancestry would improve future confirmation of ancestry-specific variants and founder effects.¹
• Structural variants were not analyzed, so the reported secondary-finding burden may be incomplete.¹
• Candidate pLOF variants require orthogonal confirmation before being treated as clinically reportable.¹

Related

• National Genetic Initiative
• Medically Actionable Secondary Findings
• Russian Ancestry Groups: Phenotype, Blood, Immunity, and Disease Differences
• Markelova et al. 2025 Genetic Heterogeneity of T2D Across Russian Ancestry Groups

Sources

• Suvorova et al. 2026, https://doi.org/10.3390/ijms27125344

Footnotes

1. extracted; from Suvorova et al. 2026, https://doi.org/10.3390/ijms27125344 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²²

2. inferred; from Suvorova et al. 2026, https://doi.org/10.3390/ijms27125344 ↩ ↩²