RAD51C
Chr 17ARRAD51 paralog C
Also known as: BROVCA3, FANCO, R51H3, RAD51L2
The RAD51C protein is essential for homologous recombination DNA repair, functioning in RAD51 paralog complexes to repair double-strand DNA breaks and resolve Holliday junctions. Autosomal recessive mutations cause Fanconi anemia complementation group O, while the gene also confers susceptibility to familial breast-ovarian cancer. This gene is extremely intolerant of loss-of-function variants (pLI near 1.0), indicating strong evolutionary constraint.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 57 | 0 | 21 | 0 | 78 |
Likely Pathogenic | 33 | 6 | 15 | 0 | 54 |
VUS | 5 | 135 | 32 | 4 | 176 |
Likely Benign | 0 | 17 | 89 | 69 | 175 |
Benign | 1 | 23 | 11 | 40 | 75 |
Conflicting | — | 34 | |||
| Total | 96 | 181 | 168 | 113 | 592 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAD51C · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies
RECRUITINGComprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO
ACTIVE NOT RECRUITINGLow Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion
ACTIVE NOT RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGA Bidirectional Cohort Study on Prophylactic Resection Surgery in Populations at Moderate-to-High Risk for Hereditary Ovarian Cancer
RECRUITINGTUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention
RECRUITINGEvaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study
RECRUITINGAn Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results
RECRUITINGPopulation Based Germline Testing for Early Detection and Prevention of Cancer
RECRUITINGSurgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
ACTIVE NOT RECRUITINGPHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
RECRUITINGAdapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
RECRUITINGExternal Resources
Links to major genomics databases and tools