BRCA1 (P38398) variants and mutations
BRCA1 (also known as P38398) is a human protein-coding gene encoding a breast cancer type 1 susceptibility protein. It coordinates DNA-damage signaling and homologous-recombination repair while helping protect stalled replication forks and chromosome integrity. Germline loss-of-function variants strongly predispose to breast and ovarian cancer and increase risk for several other malignancies. This analysis covers 9,743 BRCA1 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes breast cancer, hereditary breast ovarian cancer syndrome, and Fanconi anemia, complementation group S. Example BRCA1 variants include D2A, D2E, and D2G.
Variant analysis overview
- Gene: BRCA1
- Protein: P38398
- UniProt accession: P38398
- Organism: Homo sapiens
- Variants analyzed: 9743
- Variant scope: all variants
- Completed: 2026-10-25
Variant and mutation evidence
- Variant composition: 9,701 unspecified-consequence records; 41 synonymous variants; 4 frameshift variants; 2 in-frame deletions; 4 missense variants; 1 in-frame insertions; 1 protein altering variant; 7 splice-region variants; 1 substitution
- Prediction scores: 9,546 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: breast cancer, hereditary breast ovarian cancer syndrome, Fanconi anemia, complementation group S, ovarian cancer, breast neoplasm, breast-ovarian cancer, familial, susceptibility to, 1, ovarian neoplasm, cancer, breast carcinoma, neoplasm, BRCA1-related cancer predisposition, hereditary breast carcinoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 30 post-translational modification sites.
- Structural context: 1,238 variants have structural context.
- PTM context: 134 variants overlap post-translational modification sites.
- Experimental data: 303 protein positions have experimental scores. Source: Enrich2 nucleotide variant scores for BRCA1 E3, Enrich2 amino acid variant scores for BRCA1 E3, Enrich2 nucleotide variant scores for BRCA1 Y2H.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Diseases linked to BRCA1
Notable BRCA1 variants
Examples include D2A, D2E, D2G, D2H, D2N, D2V, D2Y, L3*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D2A (p.Asp2Ala), rs2055745664, ClinGen CA10602149, ClinVar RCV001077627, Ensembl rs2055745664, ESM-1b 1.00, AlphaMissense 0.34, Uncertain significance
- D2E (p.Asp2Glu), rs754763517, ClinGen CA10602145, ClinVar RCV001078093, ExAC rs754763517, ESM-1b 0.00, AlphaMissense 0.31, Likely benign
- D2G (p.Asp2Gly), rs2055745664, ClinGen CA10602148, ClinVar RCV001077628, ClinVar RCV001372200, ESM-1b 1.00, AlphaMissense 0.30, Uncertain significance, Hereditary breast ovarian cancer syndrome
- D2H (p.Asp2His), rs778775133, ClinGen CA10602151, ClinVar RCV001077625, ExAC rs778775133, ESM-1b 1.00, AlphaMissense 0.48, Likely benign
- D2N (p.Asp2Asn), rs778775133, ClinGen CA056202, ClinVar RCV001077624, ClinVar RCV005520432, REVEL 0.53, ESM-1b 0.00, Likely benign, Hereditary cancer-predisposing syndrome
- D2V (p.Asp2Val), rs2055745664, ClinGen CA10602147, ClinVar RCV001077629, Ensembl rs2055745664, ESM-1b 1.00, AlphaMissense 0.43, Uncertain significance
- D2Y (p.Asp2Tyr), rs778775133, ClinGen CA10602150, ClinVar RCV001077626, ExAC rs778775133, ESM-1b 1.00, AlphaMissense 0.32, Likely benign
- L3* (p.Leu3Ter), rs397509332, ClinGen CA003956, ClinVar RCV000562883, ClinVar RCV000577822, CADD 36.00, Pathogenic
- L3F (p.Leu3Phe), rs780157871, ClinGen CA10602140, ClinVar RCV000509994, ClinVar RCV001037875, ESM-1b 0.00, AlphaMissense 0.08, Likely benign
- L3I (p.Leu3Ile), rs2055745032, ClinGen CA10602144, ClinVar RCV001078094, Ensembl rs2055745032, ESM-1b 0.00, AlphaMissense 0.07, Breast-ovarian cancer, familial, susceptibility
- L3S (p.Leu3Ser), rs397509332, ClinGen CA059922, ClinVar RCV001078098, ClinVar RCV001873443, REVEL 0.55, ESM-1b 0.00, Uncertain significance, Hereditary breast ovarian cancer syndrome
- L3V (p.Leu3Val), rs2055745032, ClinGen CA10602143, ClinVar RCV001078096, Ensembl rs2055745032, ESM-1b 0.00, AlphaMissense 0.07, Breast-ovarian cancer, familial, susceptibility
- S4A (p.Ser4Ala), rs876658707, ClinGen CA10602138, ClinVar RCV001072307, TOPMed rs876658707, ESM-1b 0.00, AlphaMissense 0.08, Likely benign, in BC
- S4C (p.Ser4Cys), rs786203152, ClinGen CA10602136, cosmic curated COSV58791, ClinVar RCV001072309, ESM-1b 1.00, AlphaMissense 0.12, Uncertain significance, in BC
- S4F (p.Ser4Phe), rs786203152, ClinGen CA000789, ClinVar RCV000166336, ClinVar RCV000662889, REVEL 0.63, ESM-1b 1.00, Uncertain significance, in BC
- S4P (p.Ser4Pro), rs876658707, ClinGen CA10580715, ClinVar RCV000216237, ClinVar RCV000706715, REVEL 0.53, ESM-1b 1.00, Likely benign, in BC
- S4T (p.Ser4Thr), rs876658707, ClinGen CA10602139, ClinVar RCV001072305, TOPMed rs876658707, ESM-1b 0.00, AlphaMissense 0.10, Likely benign, in BC
- S4Y (p.Ser4Tyr), rs786203152, ClinGen CA10602137, ClinVar RCV001072308, Ensembl rs786203152, ESM-1b 1.00, AlphaMissense 0.24, Uncertain significance, in BC
- S4R (p.Ser4Arg), gnomAD 17-43050081-G-T, ESM-1b 1.00, AlphaMissense 0.57
- S4N (p.Ser4Asn), rs1490512430, gnomAD 17-43050082-C-T, ESM-1b 0.22, AlphaMissense 0.27
- S4G (p.Ser4Gly), gnomAD 17-43050089-T-C, ESM-1b 0.65, AlphaMissense 0.16
- A5G (p.Ala5Gly), rs80357287, ClinGen CA001332, NCI-TCGA Cosmic COSV5879, ClinVar RCV000077503, MetaLR 0.65, MetaSVM 0.35, Pathogenic
- A5D (p.Ala5Asp), rs1335137805, ClinGen CA10602132, ClinVar RCV001076428, gnomAD rs1335137805, ESM-1b 0.46, AlphaMissense 0.21, Likely benign
- A5P (p.Ala5Pro), rs1597923713, ClinGen CA10602134, ClinVar RCV001011371, ClinVar RCV001076426, ESM-1b 0.31, AlphaMissense 0.16, Uncertain significance
- A5S (p.Ala5Ser), rs1597923713, ClinGen CA10602133, ClinVar RCV001076427, Ensembl rs1597923713, ESM-1b 0.00, AlphaMissense 0.10, Uncertain significance
- A5T (p.Ala5Thr), rs1597923713, ClinGen CA10602135, ClinVar RCV001076425, ClinVar RCV005359855, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance
- A5V (p.Ala5Val), rs1335137805, ClinGen CA10602130, ClinVar RCV000698926, ClinVar RCV001077640, REVEL 0.54, ESM-1b 0.00, Likely benign
- L6F (p.Leu6Phe), rs1315262605, ClinGen CA10602127, ClinVar RCV000815437, ClinVar RCV001077646, REVEL 0.45, ESM-1b 0.00, Uncertain significance
- L6H (p.Leu6His), rs2055741739, ClinGen CA10602126, ClinVar RCV001078105, Ensembl rs2055741739, ESM-1b 0.17, AlphaMissense 0.13, Likely benign
- L6I (p.Leu6Ile), rs1315262605, ClinGen CA10602129, ClinVar RCV001077644, TOPMed rs1315262605, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance
- L6P (p.Leu6Pro), rs2055741739, ClinGen CA10602125, ClinVar RCV001078106, Ensembl rs2055741739, ESM-1b 0.00, AlphaMissense 0.11, Likely benign
- L6R (p.Leu6Arg), rs2055741739, ClinGen CA10602124, ClinVar RCV001078107, ClinVar RCV001593258, ESM-1b 0.00, AlphaMissense 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; BRCA1-related cancer predisposition; He
- L6V (p.Leu6Val), rs1315262605, ClinGen CA10602128, ClinVar RCV001077645, ClinVar RCV005367716, ESM-1b 0.00, AlphaMissense 0.05, Uncertain significance, Breast-ovarian cancer, familial, susceptibility to, 1; Fanconi anemia, complemen
- L6L (p.Leu6Leu), gnomAD 17-43050066-C-A, CADD 5.80
- R7C (p.Arg7Cys), rs80356994, ClinGen CA001330, cosmic curated COSV10052, ClinVar RCV000031021, REVEL 0.56, ESM-1b 0.81, Likely benign
- R7G (p.Arg7Gly), rs80356994, ClinGen CA10602123, ClinVar RCV001078112, ESP rs80356994, ESM-1b 0.00, AlphaMissense 0.18, Likely benign
- R7H (p.Arg7His), rs144792613, ClinGen CA001390, NCI-TCGA Cosmic COSV5879, cosmic curated COSV58802, REVEL 0.53, ESM-1b 0.00, Likely benign
- R7L (p.Arg7Leu), rs144792613, ClinGen CA10602121, cosmic curated COSV58793, ClinVar RCV001014438, REVEL 0.59, ESM-1b 0.00, Likely benign
- R7P (p.Arg7Pro), rs144792613, ClinGen CA10602122, ClinVar RCV001072326, ESP rs144792613, ESM-1b 0.00, AlphaMissense 0.20, Likely benign
- R7S (p.Arg7Ser), rs80356994, ClinGen CA054990, ClinVar RCV000637702, ClinVar RCV001078111, REVEL 0.50, ESM-1b 0.00, Likely benign
- V8A (p.Val8Ala), rs2055739664, ClinGen CA10602117, ClinVar RCV001076438, ClinVar RCV002258132, ESM-1b 0.00, AlphaMissense 0.25, Uncertain significance
- V8D (p.Val8Asp), rs2055739664, ClinGen CA10602118, ClinVar RCV001076437, ClinVar RCV003238837, ESM-1b 1.00, AlphaMissense 0.49, Uncertain significance
- V8F (p.Val8Phe), rs528902306, ClinGen CA10602119, cosmic curated COSV10439, ClinVar RCV001076436, ESM-1b 0.86, AlphaMissense 0.23, Likely benign
- V8G (p.Val8Gly), rs2055739664, ClinGen CA10602116, ClinVar RCV001076439, Ensembl rs2055739664, ESM-1b 1.00, AlphaMissense 0.26, Uncertain significance
- V8I (p.Val8Ile), rs528902306, ClinGen CA055451, cosmic curated COSV10052, ClinVar RCV000573882, REVEL 0.50, ESM-1b 0.00, Likely benign
- V8L (p.Val8Leu), rs528902306, ClinGen CA10602120, ClinVar RCV001076435, 1000Genomes rs528902306, ESM-1b 0.00, AlphaMissense 0.32, Likely benign
- E9* (p.Glu9Ter), rs1567823437, ClinGen CA10602113, ClinVar RCV001077656, Ensembl rs1567823437, MetaLR 0.55, MetaSVM -0.05, Likely pathogenic
- E9A (p.Glu9Ala), rs2055738683, ClinGen CA10602112, ClinVar RCV001077657, Ensembl rs2055738683, ESM-1b 0.00, AlphaMissense 0.19, Breast-ovarian cancer, familial, susceptibility
- E9D (p.Glu9Asp), rs2055738370, ClinGen CA10602108, ClinVar RCV001078113, Ensembl rs2055738370, ESM-1b 0.00, AlphaMissense 0.22, Likely benign
- E9G (p.Glu9Gly), rs2055738683, ClinGen CA10602111, ClinVar RCV001077658, Ensembl rs2055738683, ESM-1b 0.00, AlphaMissense 0.15, Breast-ovarian cancer, familial, susceptibility
- E9K (p.Glu9Lys), rs1567823437, ClinGen CA10602115, ClinVar RCV001077654, Ensembl rs1567823437, ESM-1b 0.00, AlphaMissense 0.19, Uncertain significance
- E9Q (p.Glu9Gln), rs1567823437, ClinGen CA10602114, NCI-TCGA Cosmic COSV5878, cosmic curated COSV58789, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance
- E9V (p.Glu9Val), rs2055738683, ClinGen CA10602110, ClinVar RCV001077659, Ensembl rs2055738683, ESM-1b 0.00, AlphaMissense 0.31, Breast-ovarian cancer, familial, susceptibility
- E10* (p.Glu10Ter), rs2055737833, ClinGen CA10602105, ClinVar RCV001078116, Ensembl rs2055737833, MetaLR 0.57, MetaSVM 0.17, Uncertain significance, in BC and BROVCA1
- E10A (p.Glu10Ala), rs2055737507, ClinGen CA10602104, ClinVar RCV001078117, Ensembl rs2055737507, ESM-1b 1.00, AlphaMissense 0.33, Uncertain significance, in BC and BROVCA1
- E10D (p.Glu10Asp), rs2055737161, ClinGen CA10602100, ClinVar RCV001072345, Ensembl rs2055737161, REVEL 0.60, ESM-1b 0.00, Breast-ovarian cancer, familial, susceptibility, in BC and BROVCA1
- E10G (p.Glu10Gly), rs2055737507, ClinGen CA10602103, ClinVar RCV001078118, ClinVar RCV003645196, ESM-1b 0.98, AlphaMissense 0.38, Uncertain significance, Hereditary breast ovarian cancer syndrome
- E10K (p.Glu10Lys), rs2055737833, ClinGen CA10602107, ClinVar RCV001078114, ClinVar RCV001797819, ESM-1b 1.00, AlphaMissense 0.45, Uncertain significance, Hereditary cancer-predisposing syndrome; BRCA1-related cancer predisposition; no
- E10Q (p.Glu10Gln), rs2055737833, ClinGen CA10602106, ClinVar RCV001078115, Ensembl rs2055737833, ESM-1b 0.65, AlphaMissense 0.37, Uncertain significance, in BC and BROVCA1
- E10V (p.Glu10Val), rs2055737507, ClinGen CA10602102, ClinVar RCV001078119, Ensembl rs2055737507, ESM-1b 1.00, AlphaMissense 0.53, Uncertain significance, in BC and BROVCA1
- V11A (p.Val11Ala), rs80357017, ClinGen CA002131, ClinVar RCV000111609, ClinVar RCV001019782, ESM-1b 1.00, AlphaMissense 0.80, Likely pathogenic
- V11E (p.Val11Glu), rs80357017, ClinGen CA10602096, ClinVar RCV001072349, Ensembl rs80357017, ESM-1b 1.00, AlphaMissense 0.84, Likely pathogenic
- V11G (p.Val11Gly), rs80357017, ClinGen CA10584577, ClinVar RCV000236530, ClinVar RCV000509835, ESM-1b 1.00, AlphaMissense 0.70, Likely pathogenic
- V11I (p.Val11Ile), rs1555601019, ClinGen CA10602099, ClinVar RCV001072346, ClinVar RCV005408681, ESM-1b 0.00, AlphaMissense 0.22, Likely benign
- V11L (p.Val11Leu), rs1555601019, ClinGen CA10602097, ClinVar RCV001072348, Ensembl rs1555601019, REVEL 0.68, ESM-1b 1.00, Uncertain significance, Hereditary breast ovarian cancer syndrome
- Q12* (p.Gln12Ter), rs80357134, ClinGen CA002251, ClinVar RCV000111614, ClinVar RCV000412855, MetaLR 0.46, MetaSVM -0.13, Pathogenic
- Q12E (p.Gln12Glu), rs80357134, ClinGen CA10602094, ClinVar RCV000801423, ClinVar RCV001076453, ESM-1b 1.00, AlphaMissense 0.13, Pathogenic
- Q12H (p.Gln12His), rs763230080, ClinGen CA10602090, ClinVar RCV001077669, ExAC rs763230080, ESM-1b 1.00, AlphaMissense 0.49, Likely benign
- Q12K (p.Gln12Lys), rs80357134, ClinGen CA10602095, ClinVar RCV001076452, ClinVar RCV004031198, REVEL 0.56, ESM-1b 0.18, Pathogenic
- Q12L (p.Gln12Leu), rs1555601006, ClinGen CA10602091, ClinVar RCV001077668, ClinVar RCV006666762, ESM-1b 1.00, AlphaMissense 0.33, Likely benign, Hereditary cancer-predisposing syndrome
- Q12P (p.Gln12Pro), rs1555601006, ClinGen CA10602093, ClinVar RCV001076454, ClinVar RCV001351289, REVEL 0.67, ESM-1b 1.00, Likely pathogenic
- Q12R (p.Gln12Arg), rs1555601006, ClinGen CA10602092, ClinVar RCV000510066, ClinVar RCV001076455, REVEL 0.58, ESM-1b 0.73, Likely pathogenic
- Q12Q (p.Gln12Gln), gnomAD 17-43050063-T-C, CADD 6.43
- N13D (p.Asn13Asp), rs1597923586, ClinGen CA10602087, ClinVar RCV000824522, ClinVar RCV001077672, ESM-1b 1.00, AlphaMissense 0.15, Likely benign
- N13H (p.Asn13His), rs1597923586, ClinGen CA10602088, ClinVar RCV001077671, Ensembl rs1597923586, ESM-1b 1.00, AlphaMissense 0.14, Likely benign
- N13I (p.Asn13Ile), rs2055733986, ClinGen CA10602083, ClinVar RCV001078122, Ensembl rs2055733986, ESM-1b 1.00, AlphaMissense 0.31, Breast-ovarian cancer, familial, susceptibility
- N13K (p.Asn13Lys), rs2055733269, ClinGen CA10602082, ClinVar RCV001078123, ClinVar RCV004601371, REVEL 0.55, ESM-1b 1.00, Likely benign, Hereditary cancer-predisposing syndrome
- N13S (p.Asn13Ser), rs2055733986, ClinGen CA10602084, ClinVar RCV001078121, Ensembl rs2055733986, ESM-1b 0.00, AlphaMissense 0.12, Breast-ovarian cancer, familial, susceptibility
- N13T (p.Asn13Thr), rs2055733986, ClinGen CA10602085, ClinVar RCV001077674, Ensembl rs2055733986, ESM-1b 0.00, AlphaMissense 0.16, Breast-ovarian cancer, familial, susceptibility
- N13Y (p.Asn13Tyr), rs1597923586, ClinGen CA10602086, ClinVar RCV001077673, Ensembl rs1597923586, ESM-1b 1.00, AlphaMissense 0.20, Likely benign
- V14A (p.Val14Ala), rs2055732014, ClinGen CA10602076, ClinVar RCV001072360, ClinVar RCV001683731, ESM-1b 0.56, AlphaMissense 0.65, Uncertain significance
- V14D (p.Val14Asp), rs2055732014, ClinGen CA10602077, cosmic curated COSV10462, ClinVar RCV001072359, REVEL 0.69, ESM-1b 1.00, Uncertain significance
- V14F (p.Val14Phe), rs2055732548, ClinGen CA10602078, ClinVar RCV001052786, ClinVar RCV001078128, REVEL 0.61, ESM-1b 1.00, Likely benign
- V14G (p.Val14Gly), rs2055732014, ClinGen CA10602075, ClinVar RCV001072361, Ensembl rs2055732014, ESM-1b 1.00, AlphaMissense 0.71, Uncertain significance
- V14I (p.Val14Ile), rs2055732548, ClinGen CA10602080, ClinVar RCV001078126, ClinVar RCV005520438, ESM-1b 0.00, AlphaMissense 0.16, Likely benign, Hereditary cancer-predisposing syndrome
- V14L (p.Val14Leu), rs2055732548, ClinGen CA10602079, ClinVar RCV001078127, Ensembl rs2055732548, REVEL 0.60, ESM-1b 0.00, Likely benign
- I15F (p.Ile15Phe), rs80357031, ClinGen CA10602073, ClinVar RCV001076463, TOPMed rs80357031, ESM-1b 0.57, AlphaMissense 0.42, Likely benign
- I15L (p.Ile15Leu), rs80357031, ClinGen CA002823, ClinVar RCV000111636, ClinVar RCV000132290, REVEL 0.45, ESM-1b 0.00, Likely benign
- I15M (p.Ile15Met), rs2055730198, ClinGen CA10602070, ClinVar RCV001076468, Ensembl rs2055730198, ESM-1b 0.00, AlphaMissense 0.19, Breast-ovarian cancer, familial, susceptibility
- I15N (p.Ile15Asn), rs80357316, ClinGen CA10602072, ClinVar RCV001076464, Ensembl rs80357316, ESM-1b 1.00, AlphaMissense 0.90, Uncertain significance
- I15S (p.Ile15Ser), rs80357316, ClinGen CA10602071, ClinVar RCV001076465, Ensembl rs80357316, ESM-1b 1.00, AlphaMissense 0.92, Uncertain significance
- I15T (p.Ile15Thr), rs80357316, ClinGen CA002886, ClinVar RCV000111641, ClinVar RCV000582098, REVEL 0.59, ESM-1b 0.61, Uncertain significance
- I15V (p.Ile15Val), rs80357031, ClinGen CA10602074, ClinVar RCV001072363, ClinVar RCV001224243, REVEL 0.44, ESM-1b 0.00, Likely benign
- N16D (p.Asn16Asp), rs2055729884, ClinGen CA10602068, ClinVar RCV001077679, ClinVar RCV005520433, ESM-1b 0.93, AlphaMissense 0.15, Likely benign, Hereditary cancer-predisposing syndrome
- N16H (p.Asn16His), rs2055729884, ClinGen CA10602069, cosmic curated COSV10963, ClinVar RCV001076469, ESM-1b 0.65, AlphaMissense 0.08, Likely benign
- N16I (p.Asn16Ile), rs2055729319, ClinGen CA10602064, ClinVar RCV001077683, Ensembl rs2055729319, ESM-1b 0.00, AlphaMissense 0.21, Breast-ovarian cancer, familial, susceptibility
- N16K (p.Asn16Lys), rs1555600963, ClinGen CA10602062, ClinVar RCV001077686, Ensembl rs1555600963, ESM-1b 0.91, AlphaMissense 0.26, Likely benign
- N16S (p.Asn16Ser), rs2055729319, ClinGen CA10602065, ClinVar RCV001077682, Ensembl rs2055729319, ESM-1b 0.00, AlphaMissense 0.08, Breast-ovarian cancer, familial, susceptibility
- N16T (p.Asn16Thr), rs2055729319, ClinGen CA10602066, ClinVar RCV001077681, Ensembl rs2055729319, ESM-1b 0.00, AlphaMissense 0.12, Breast-ovarian cancer, familial, susceptibility
- N16Y (p.Asn16Tyr), rs2055729884, ClinGen CA10602067, ClinVar RCV001077680, Ensembl rs2055729884, ESM-1b 0.27, AlphaMissense 0.13, Likely benign
- A17D (p.Ala17Asp), rs1412871417, ClinGen CA10602058, ClinVar RCV001078132, TOPMed rs1412871417, ESM-1b 0.33, AlphaMissense 0.59, Uncertain significance
- A17G (p.Ala17Gly), rs1412871417, ClinGen CA10602057, ClinVar RCV001078133, TOPMed rs1412871417, ESM-1b 0.00, AlphaMissense 0.25, Uncertain significance, Breast-ovarian cancer, familial, susceptibility to, 1
- A17P (p.Ala17Pro), rs1402064476, ClinGen CA10602060, ClinVar RCV001078130, TOPMed rs1402064476, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Breast-ovarian cancer, familial, susceptibility to, 1
- A17S (p.Ala17Ser), rs1402064476, ClinGen CA10602059, ClinVar RCV000580266, ClinVar RCV001078131, ESM-1b 0.00, AlphaMissense 0.17, Uncertain significance
- A17T (p.Ala17Thr), rs1402064476, ClinGen CA10602061, ClinVar RCV001078129, TOPMed rs1402064476, ESM-1b 0.00, AlphaMissense 0.24, Uncertain significance
- A17V (p.Ala17Val), rs1412871417, ClinGen CA10602056, ClinVar RCV001078134, TOPMed rs1412871417, ESM-1b 0.00, AlphaMissense 0.44, Uncertain significance
- M18I (p.Met18Ile), rs1597923450, ClinGen CA10602049, ClinVar RCV001076478, ClinVar RCV005401726, REVEL 0.68, ESM-1b 1.00, Likely benign, in BC
- M18K (p.Met18Lys), rs80356929, ClinGen CA003549, ClinVar RCV000111654, ClinVar RCV000496411, ESM-1b 1.00, AlphaMissense 0.96, Pathogenic, in BC
- M18L (p.Met18Leu), rs2055727017, ClinGen CA10602055, ClinVar RCV001072372, ClinVar RCV004031172, ESM-1b 0.49, AlphaMissense 0.49, Likely benign, in BC
- M18R (p.Met18Arg), rs80356929, ClinGen CA10602052, ClinVar RCV000637401, ClinVar RCV001072375, ESM-1b 1.00, AlphaMissense 0.96, Pathogenic, in BC
- M18T (p.Met18Thr), rs80356929, ClinGen CA003550, ClinVar RCV000031245, ClinVar RCV000131693, REVEL 0.77, ESM-1b 1.00, Pathogenic, in BC
- M18V (p.Met18Val), rs2055727017, ClinGen CA10602054, ClinVar RCV001072373, ClinVar RCV001264576, ESM-1b 1.00, AlphaMissense 0.49, Likely benign, in BC
- Q19* (p.Gln19Ter), rs397509299, ClinGen CA003737, ClinVar RCV000256854, ClinVar RCV001185214, MetaLR 0.75, MetaSVM 0.61, Pathogenic
- Q19E (p.Gln19Glu), rs397509299, ClinGen CA10602047, ClinVar RCV001076480, ClinVar RCV001374272, ESM-1b 0.00, AlphaMissense 0.19, Pathogenic
- Q19H (p.Gln19His), rs2055725365, ClinGen CA10602042, ClinVar RCV001077697, Ensembl rs2055725365, ESM-1b 0.00, AlphaMissense 0.79, Variant assessed as somatic; moderate impact.
- Q19K (p.Gln19Lys), rs397509299, ClinGen CA10602048, ClinVar RCV001076479, Ensembl rs397509299, ESM-1b 0.00, AlphaMissense 0.21, Pathogenic
- Q19L (p.Gln19Leu), rs2055725680, ClinGen CA10602044, ClinVar RCV001076483, Ensembl rs2055725680, ESM-1b 1.00, AlphaMissense 0.48, Likely pathogenic
- Q19P (p.Gln19Pro), rs2055725680, ClinGen CA10602046, ClinVar RCV001076481, ClinVar RCV001340949, ESM-1b 1.00, AlphaMissense 0.95, Likely pathogenic
- Q19R (p.Gln19Arg), rs2055725680, ClinGen CA10602045, ClinVar RCV001071148, ClinVar RCV001076482, ESM-1b 0.00, AlphaMissense 0.29, Likely pathogenic
- K20* (p.Lys20Ter), rs2055725050, ClinGen CA10602039, ClinVar RCV001077700, Ensembl rs2055725050, MetaLR 0.66, MetaSVM 0.39, Uncertain significance
- K20E (p.Lys20Glu), rs2055725050, ClinGen CA10602040, ClinVar RCV001077699, ClinVar RCV001241842, ESM-1b 1.00, AlphaMissense 0.63, Uncertain significance, Hereditary breast ovarian cancer syndrome
- K20I (p.Lys20Ile), rs2055724752, ClinGen CA10602036, ClinVar RCV001077745, Ensembl rs2055724752, ESM-1b 1.00, AlphaMissense 0.85, Breast-ovarian cancer, familial, susceptibility
- K20N (p.Lys20Asn), rs202168814, ClinGen CA003760, ClinVar RCV000159933, ClinVar RCV000215880, ESM-1b 1.00, AlphaMissense 0.81, Likely benign
- K20Q (p.Lys20Gln), rs2055725050, ClinGen CA10602041, ClinVar RCV001077698, Ensembl rs2055725050, ESM-1b 1.00, AlphaMissense 0.55, Uncertain significance
- K20R (p.Lys20Arg), rs2055724752, ClinGen CA10602037, ClinVar RCV001077702, Ensembl rs2055724752, ESM-1b 0.51, AlphaMissense 0.19, Breast-ovarian cancer, familial, susceptibility
- K20T (p.Lys20Thr), rs2055724752, ClinGen CA10602038, ClinVar RCV001077701, Ensembl rs2055724752, ESM-1b 1.00, AlphaMissense 0.67, Breast-ovarian cancer, familial, susceptibility
- I21F (p.Ile21Phe), rs80357406, ClinGen CA10602033, ClinVar RCV001077750, ExAC rs80357406, ESM-1b 0.00, AlphaMissense 0.50, Likely benign
- I21L (p.Ile21Leu), rs80357406, ClinGen CA10602034, ClinVar RCV001077749, ClinVar RCV004031210, ESM-1b 0.00, AlphaMissense 0.32, Likely benign, Hereditary cancer-predisposing syndrome
- I21M (p.Ile21Met), rs1555600921, ClinGen CA10602029, ClinVar RCV001072388, ClinVar RCV001862477, ESM-1b 0.00, AlphaMissense 0.30, Uncertain significance, Hereditary breast ovarian cancer syndrome
- I21N (p.Ile21Asn), rs1135401834, ClinGen CA10602032, ClinVar RCV001077751, Ensembl rs1135401834, ESM-1b 0.05, AlphaMissense 0.38, Likely benign
- I21S (p.Ile21Ser), rs1135401834, ClinGen CA10602030, ClinVar RCV000496697, ClinVar RCV001072386, ESM-1b 0.00, AlphaMissense 0.73, Likely benign
- I21T (p.Ile21Thr), rs1135401834, ClinGen CA10602031, ClinVar RCV001072385, ClinVar RCV004950263, ESM-1b 0.00, AlphaMissense 0.75, Likely benign
- I21V (p.Ile21Val), rs80357406, ClinGen CA003764, ClinVar RCV000111663, ClinVar RCV000131702, REVEL 0.61, ESM-1b 0.00, Likely benign
- L22* (p.Leu22Ter), rs80357438, ClinGen CA10585945, ClinVar RCV000239088, ClinVar RCV000660988, MetaLR 0.79, MetaSVM 0.67, Pathogenic, in BC
- L22F (p.Leu22Phe), rs786202533, ClinGen CA003790, ClinVar RCV000165382, ClinVar RCV001076493, ESM-1b 0.00, AlphaMissense 0.83, Likely benign, in BC
- L22I (p.Leu22Ile), rs1597923402, ClinGen CA10602028, ClinVar RCV001072390, Ensembl rs1597923402, ESM-1b 1.00, AlphaMissense 0.56, Likely benign, in BC
- L22S (p.Leu22Ser), rs80357438, ClinGen CA003779, ClinVar RCV000049081, ClinVar RCV000083224, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic, in BC
- L22V (p.Leu22Val), rs1597923402, ClinGen CA10602027, ClinVar RCV001072392, Ensembl rs1597923402, ESM-1b 1.00, AlphaMissense 0.58, Likely benign, in BC
- E23* (p.Glu23Ter), rs372047427, ClinGen CA10602022, ClinVar RCV001077710, ClinVar RCV002365789, MetaLR 0.59, MetaSVM 0.23, Pathogenic, in BC and BROVCA1
- E23A (p.Glu23Ala), rs1597923307, ClinGen CA10602021, ClinVar RCV001025778, ClinVar RCV001077711, REVEL 0.79, ESM-1b 1.00, Uncertain significance, in BC and BROVCA1
- E23D (p.Glu23Asp), rs766004110, ClinGen CA10580714, ClinVar RCV000218588, ClinVar RCV000462185, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Hereditary cancer-predisposing syndrome
- E23G (p.Glu23Gly), rs1597923307, ClinGen CA10602020, ClinVar RCV001077712, Ensembl rs1597923307, ESM-1b 1.00, AlphaMissense 0.88, Uncertain significance, in BC and BROVCA1
- E23K (p.Glu23Lys), rs372047427, ClinGen CA10602024, ClinVar RCV001076496, ClinVar RCV003584826, ESM-1b 1.00, AlphaMissense 0.95, Pathogenic, in BC and BROVCA1
- E23Q (p.Glu23Gln), rs372047427, ClinGen CA10602023, ClinVar RCV000510068, ClinVar RCV001076497, REVEL 0.68, ESM-1b 1.00, Pathogenic, in BC and BROVCA1
- E23V (p.Glu23Val), rs1597923307, ClinGen CA10602019, ClinVar RCV001077713, Ensembl rs1597923307, ESM-1b 1.00, AlphaMissense 0.92, Uncertain significance, in BC and BROVCA1
- C24* (p.Cys24Ter), rs1597923232, ClinGen CA10602013, ClinVar RCV001077755, ClinVar RCV005093446, Pathogenic
- C24F (p.Cys24Phe), rs80357198, ClinGen CA10602014, cosmic curated COSV58794, ClinVar RCV001077754, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic
- C24G (p.Cys24Gly), rs80357410, ClinGen CA10602016, ClinVar RCV000804266, ClinVar RCV001077752, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic
- C24R (p.Cys24Arg), rs80357410, ClinGen CA003829, ClinVar RCV000111679, ClinVar RCV000586566, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic
- C24S (p.Cys24Ser), rs80357198, ClinGen CA10602015, ClinVar RCV001077753, ClinVar RCV002222196, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Hereditary breast ovarian cancer syndrome
- C24W (p.Cys24Trp), rs1597923232, ClinGen CA10602012, cosmic curated COSV10736, ClinVar RCV000807975, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic
- C24Y (p.Cys24Tyr), rs80357198, ClinGen CA003834, cosmic curated COSV10736, ClinVar RCV000111685, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic
- P25A (p.Pro25Ala), rs397509313, ClinGen CA10602011, ClinVar RCV001072402, Ensembl rs397509313, ESM-1b 1.00, AlphaMissense 0.93, Uncertain significance
- P25H (p.Pro25His), Ensembl rs876660096, ESM-1b 1.00, AlphaMissense 0.97, Likely pathogenic
- P25L (p.Pro25Leu), rs876660096, ClinGen CA10580713, ClinVar RCV000223256, ClinVar RCV000227670, REVEL 0.84, ESM-1b 1.00, Likely pathogenic
- P25R (p.Pro25Arg), rs876660096, ClinGen CA10602008, ClinVar RCV001072404, Ensembl rs876660096, ESM-1b 1.00, AlphaMissense 0.96, Likely pathogenic
- P25S (p.Pro25Ser), rs397509313, ClinGen CA10602010, ClinVar RCV001072403, Ensembl rs397509313, ESM-1b 0.00, AlphaMissense 0.95, Uncertain significance
- P25T (p.Pro25Thr), rs397509313, ClinGen CA003845, cosmic curated COSV10052, ClinVar RCV000577370, REVEL 0.82, ESM-1b 0.55, Uncertain significance
- I26F (p.Ile26Phe), rs1597923170, ClinGen CA10602005, ClinVar RCV001026728, ClinVar RCV001300316, ESM-1b 1.00, AlphaMissense 0.93, Uncertain significance
- I26L (p.Ile26Leu), rs1597923170, ClinGen CA10602007, ClinVar RCV001072406, Ensembl rs1597923170, ESM-1b 1.00, AlphaMissense 0.69, Uncertain significance
- I26M (p.Ile26Met), rs1555600862, ClinGen CA10602002, ClinVar RCV001076509, ClinVar RCV005782093, ESM-1b 1.00, AlphaMissense 0.84, Likely benign
- I26N (p.Ile26Asn), rs879255496, ClinGen CA10586118, ClinVar RCV000239011, Ensembl rs879255496, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic
- I26S (p.Ile26Ser), rs879255496, ClinGen CA10602003, ClinVar RCV001076507, Ensembl rs879255496, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic
- I26T (p.Ile26Thr), rs879255496, ClinGen CA10602004, ClinVar RCV001061570, ClinVar RCV001076506, REVEL 0.81, ESM-1b 1.00, Pathogenic
- I26V (p.Ile26Val), rs1597923170, ClinGen CA10602006, ClinVar RCV001072407, Ensembl rs1597923170, ESM-1b 0.26, AlphaMissense 0.23, Uncertain significance
- C27* (p.Cys27Ter), rs587780805, ClinGen CA10601991, ClinVar RCV001076155, gnomAD rs587780805, Likely pathogenic
- C27F (p.Cys27Phe), rs1064793052, ClinGen CA10601996, ClinVar RCV000561214, ClinVar RCV000696469, REVEL 0.96, ESM-1b 1.00, Likely pathogenic
- C27G (p.Cys27Gly), rs2055713838, ClinGen CA10601999, ClinVar RCV001076513, ClinVar RCV005782094, ESM-1b 1.00, AlphaMissense 0.98, Likely pathogenic
- C27R (p.Cys27Arg), rs2055713838, ClinGen CA10602000, ClinVar RCV001076512, ClinVar RCV005318613, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic
- C27S (p.Cys27Ser), rs1064793052, ClinGen CA10601997, ClinVar RCV000480934, ClinVar RCV001077722, ESM-1b 1.00, AlphaMissense 0.99, Likely pathogenic
- C27W (p.Cys27Trp), rs587780805, ClinGen CA10601990, ClinVar RCV001076156, ClinVar RCV005520423, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic
- C27Y (p.Cys27Tyr), rs1064793052, ClinGen CA10601998, ClinVar RCV001027178, ClinVar RCV001049303, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic
- L28M (p.Leu28Met), rs1219301058, ClinGen CA10601989, ClinVar RCV001076157, ClinVar RCV002554778, ESM-1b 1.00, AlphaMissense 0.61, Likely benign
- L28P (p.Leu28Pro), rs80357266, ClinGen CA003933, ClinVar RCV000077631, ClinVar RCV000588761, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance
- L28Q (p.Leu28Gln), rs80357266, ClinGen CA10601987, ClinVar RCV001076552, Ensembl rs80357266, ESM-1b 1.00, AlphaMissense 0.92, Uncertain significance
- L28R (p.Leu28Arg), rs80357266, ClinGen CA10601986, ClinVar RCV001076553, Ensembl rs80357266, ESM-1b 1.00, AlphaMissense 0.81, Uncertain significance
- L28V (p.Leu28Val), rs1219301058, ClinGen CA10601988, ClinVar RCV001027380, ClinVar RCV001076550, ESM-1b 1.00, AlphaMissense 0.76, Likely benign
- E29* (p.Glu29Ter), rs80357443, ClinGen CA003943, ClinVar RCV000031288, ClinVar RCV001389948, MetaLR 0.74, MetaSVM 0.56, Pathogenic
- E29A (p.Glu29Ala), rs773841328, ClinGen CA10601983, ClinVar RCV001076954, ExAC rs773841328, ESM-1b 1.00, AlphaMissense 0.71, Likely benign
- E29D (p.Glu29Asp), rs1343667553, ClinGen CA10601981, ClinVar RCV001076958, TOPMed rs1343667553, ESM-1b 0.00, AlphaMissense 0.37, Likely benign
Public BRCA1 analysis runs
- BRCA1 analysis run — BRCA1 (9,743 variants) — completed 2026-10-25
- BRCA1 analysis run — BRCA1 (9,768 variants) — completed 2026-08-09