CACNB2 (Q08289) variants and mutations
CACNB2 (also known as Q08289) is a human protein-coding gene encoding a voltage-dependent L-type calcium channel subunit beta-2 protein. It regulates gating and membrane delivery of high-voltage-activated calcium channels, including cardiac Cav1.2. Rare pathogenic variants have been associated with cardiac arrhythmia and neurodevelopmental phenotypes, although variant-specific evidence is important when interpreting causality. This analysis covers 1,243 CACNB2 variants and mutations. Of these, 72% have computational variant effect predictions. Disease context includes epilepsy, neuropathic pain, and fibromyalgia. Example CACNB2 variants include M1I, M1V, and V2A.
Variant analysis overview
- Gene: CACNB2
- Protein: Q08289
- UniProt accession: Q08289
- Organism: Homo sapiens
- Variants analyzed: 1243
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 1,113 unspecified-consequence records; 33 synonymous variants; 4 frameshift variants; 80 missense variants; 7 stop-gained variants; 2 in-frame insertions; 3 in-frame deletions; 1 splice-region variants
- Prediction scores: 893 variants have prediction scores (72% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: epilepsy, neuropathic pain, fibromyalgia, Seizure, restless legs syndrome, postherpetic neuralgia, cardiovascular disorder, anxiety disorder, neuralgia, Brugada syndrome, Focal-onset seizure, hypertensive disorder.
Protein structure and variant hotspots
- Protein features: 1 domains; 5 post-translational modification sites.
- Structural context: 125 variants have structural context.
- PTM context: 6 variants overlap post-translational modification sites.
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, MaveDB, LitVar.
Notable CACNB2 variants
Examples include M1I, M1V, V2A, V2F, V2I, V2V, Q3R, Q3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2491183020, ClinGen CA376213741, ClinVar RCV003340730, Uncertain significance, Brugada syndrome 4
- M1V (p.Met1Val), rs746311834, ClinGen CA5429322, ClinVar RCV000455907, MetaLR 0.40, MetaSVM -0.40, Uncertain significance, not specified
- V2A (p.Val2Ala), Ensembl rs2130978397
- V2F (p.Val2Phe), ExAC rs780368829, TOPMed rs780368829, gnomAD rs780368829, REVEL 0.47, CADD 25.10, Uncertain significance
- V2I (p.Val2Ile), rs780368829, ClinGen CA376213744, ClinVar RCV004432354, ExAC rs780368829, REVEL 0.13, CADD 23.00, Uncertain significance, Cardiovascular phenotype
- V2V (p.Val2Val), gnomAD 10-18140742-C-A, CADD 11.90
- Q3R (p.Gln3Arg), TOPMed rs1424520121, gnomAD rs1424520121, REVEL 0.14, CADD 19.60
- Q3K (p.Gln3Lys), gnomAD 10-18140743-C-A, REVEL 0.11, CADD 22.60
- Q3Q (p.Gln3Gln), rs754160008, gnomAD 10-18140745-A-G, CADD 9.24
- Q3* (p.Gln3Ter), gnomAD 10-18141186-C-T, CADD 19.50
- Q3L (p.Gln3Leu), gnomAD 10-18141187-A-T, CADD 19.20
- Q3P (p.Gln3Pro), gnomAD 10-18141187-A-C, CADD 19.30
- Q3H (p.Gln3His), rs1336540034, gnomAD 10-18141188-G-T, CADD 17.70
- R4G (p.Arg4Gly), rs776609335, gnomAD 10-18140743-CA-C, CADD 22.30
- R4S (p.Arg4Ser), gnomAD 10-18140748-G-T, REVEL 0.14, CADD 21.30
- R4R (p.Arg4Arg), rs555435660, gnomAD 10-18140748-G-A, CADD 14.10
- D5Y (p.Asp5Tyr), gnomAD 10-18140749-G-T, REVEL 0.45, CADD 26.00
- D5H (p.Asp5His), gnomAD 10-18140749-G-C, REVEL 0.31, CADD 24.20
- D5G (p.Asp5Gly), gnomAD 10-18140750-A-G, REVEL 0.31, CADD 23.50
- D5D (p.Asp5Asp), gnomAD 10-18140751-C-T, CADD 12.80
- D5E (p.Asp5Glu), gnomAD 10-18140751-C-A, REVEL 0.20, CADD 22.50
- D5N (p.Asp5Asn), gnomAD 10-18141201-G-A, CADD 19.90
- D5A (p.Asp5Ala), rs1588525544, gnomAD 10-18141202-A-C, CADD 20.50
- M6S (p.Met6Ser), rs786205787, gnomAD 10-18140752-AT-A, CADD 24.20
- M6L (p.Met6Leu), gnomAD 10-18140752-A-T, REVEL 0.15, CADD 20.80
- M6T (p.Met6Thr), gnomAD 10-18140753-T-C, REVEL 0.14, CADD 22.70
- M6I (p.Met6Ile), gnomAD 10-18140754-G-C, REVEL 0.28, CADD 23.30
- S7F (p.Ser7Phe), ExAC rs779066586, TOPMed rs779066586, gnomAD rs779066586
- S7Y (p.Ser7Tyr), ExAC rs779066586, TOPMed rs779066586, gnomAD rs779066586, REVEL 0.22, CADD 23.00
- S7A (p.Ser7Ala), gnomAD 10-18140755-T-G, REVEL 0.22, CADD 20.40
- S7S (p.Ser7Ser), gnomAD 10-18140757-C-T, CADD 15.30
- S7V (p.Ser7Val), gnomAD 10-18141187-AG-A, CADD 17.00
- S7R (p.Ser7Arg), rs1307102327, gnomAD 10-18141192-A-C, CADD 19.70
- S7G (p.Ser7Gly), gnomAD 10-18141192-A-G, CADD 19.90
- S7N (p.Ser7Asn), gnomAD 10-18141193-G-A, CADD 20.00
- S7I (p.Ser7Ile), gnomAD 10-18141193-G-T, CADD 19.60
- K8* (p.Lys8Ter), ExAC rs78722981, gnomAD rs78722981, CADD 37.00
- K8E (p.Lys8Glu), ExAC rs78722981, gnomAD rs78722981, REVEL 0.27, CADD 23.40
- K8R (p.Lys8Arg), rs1564288218, Ensembl rs1564288218, AlphaMissense 0.07, MetaLR 0.18, Variant assessed as somatic; moderate impact.
- K8Q (p.Lys8Gln), gnomAD 10-18140758-A-C, REVEL 0.27, CADD 23.10
- K8K (p.Lys8Lys), gnomAD 10-18140760-G-A, CADD 14.00
- K8M (p.Lys8Met), gnomAD 10-18141211-A-T, CADD 19.20
- K8N (p.Lys8Asn), gnomAD 10-18141212-G-T, CADD 20.30
- S9L (p.Ser9Leu), ExAC rs772164191, gnomAD rs772164191, REVEL 0.28, CADD 26.50
- S9W (p.Ser9Trp), ExAC rs772164191, gnomAD rs772164191, REVEL 0.48, CADD 27.10
- S9* (p.Ser9Ter), gnomAD 10-18140762-C-A, CADD 37.00
- S9S (p.Ser9Ser), gnomAD 10-18140763-G-A, CADD 14.90
- P10S (p.Pro10Ser), NCI-TCGA TCGA novel, REVEL 0.23, CADD 23.20, Variant assessed as somatic; moderate impact.
- P10L (p.Pro10Leu), gnomAD 10-18140765-C-T, REVEL 0.20, CADD 23.70
- P10P (p.Pro10Pro), gnomAD 10-18140766-T-C, CADD 16.30
- P11S (p.Pro11Ser), ESP rs377258255, ExAC rs377258255, TOPMed rs377258255, gnomAD rs377258255, REVEL 0.18, CADD 17.60, Uncertain significance
- P11T (p.Pro11Thr), rs377258255, ESP rs377258255, ExAC rs377258255, TOPMed rs377258255, REVEL 0.12, CADD 18.00, Uncertain significance, Cardiovascular phenotype
- P11A (p.Pro11Ala), gnomAD 10-18140767-C-G, REVEL 0.15, CADD 16.50
- P11H (p.Pro11His), gnomAD 10-18140768-C-A, REVEL 0.18, CADD 22.50
- P11P (p.Pro11Pro), rs770888729, gnomAD 10-18140769-C-T, CADD 14.70
- T12R (p.Thr12Arg), 1000Genomes rs574680412, TOPMed rs574680412, gnomAD rs574680412, REVEL 0.13, CADD 22.30
- T12S (p.Thr12Ser), Ensembl rs2130978546
- T12P (p.Thr12Pro), gnomAD 10-18140770-A-C, REVEL 0.19, CADD 19.80
- T12A (p.Thr12Ala), gnomAD 10-18140770-A-G, REVEL 0.21, CADD 22.00
- T12I (p.Thr12Ile), gnomAD 10-18140771-C-T, REVEL 0.12, CADD 22.50
- A13S (p.Ala13Ser), TOPMed rs2030293456
- A13V (p.Ala13Val), Ensembl rs2130978587, REVEL 0.25, CADD 23.40
- A13E (p.Ala13Glu), gnomAD 10-18140774-C-A, REVEL 0.46, CADD 23.10
- A13G (p.Ala13Gly), gnomAD 10-18140774-C-G, REVEL 0.22, CADD 22.70
- A13A (p.Ala13Ala), gnomAD 10-18140775-G-T, CADD 14.40
- A14T (p.Ala14Thr), gnomAD rs1439539802, REVEL 0.29, CADD 15.90
- A14V (p.Ala14Val), Ensembl rs2030294364, REVEL 0.25, CADD 23.30
- A14E (p.Ala14Glu), gnomAD 10-18140777-C-A, REVEL 0.49, CADD 23.00
- A14A (p.Ala14Ala), gnomAD 10-18140778-G-T, CADD 13.60
- A15V (p.Ala15Val), rs897880041, NCI-TCGA Cosmic COSV5663, cosmic curated COSV56639, gnomAD rs897880041, REVEL 0.41, CADD 21.60, Variant assessed as somatic; moderate impact.
- p.Ala15 Ala16del, gnomAD 10-18140772-AGCGG, CADD 19.60
- A15S (p.Ala15Ser), gnomAD 10-18140779-G-T, REVEL 0.34, CADD 20.50
- A15T (p.Ala15Thr), gnomAD 10-18140779-G-A, REVEL 0.34, CADD 22.40
- A15E (p.Ala15Glu), gnomAD 10-18140780-C-A, REVEL 0.54, CADD 21.30
- A15G (p.Ala15Gly), gnomAD 10-18140780-C-G, REVEL 0.39, CADD 22.60
- A15A (p.Ala15Ala), gnomAD 10-18140781-G-T, CADD 14.30
- A16V (p.Ala16Val), cosmic curated COSV56614, gnomAD rs866894450, REVEL 0.26, CADD 23.70
- p.Ala16dup, rs759384990, gnomAD 10-18140772-A-AGC, CADD 19.40
- A16del (p.Ala16del), rs759384990, gnomAD 10-18140772-AGCG-, CADD 19.40
- A16T (p.Ala16Thr), gnomAD 10-18140782-G-A, REVEL 0.22, CADD 22.80
- A16E (p.Ala16Glu), gnomAD 10-18140783-C-A, REVEL 0.42, CADD 23.40
- A16A (p.Ala16Ala), rs776286531, gnomAD 10-18140784-G-A, CADD 14.90
- V17A (p.Val17Ala), TOPMed rs530601558, gnomAD rs530601558, REVEL 0.26, CADD 15.30
- V17G (p.Val17Gly), TOPMed rs530601558, gnomAD rs530601558, REVEL 0.48, CADD 20.20
- V17L (p.Val17Leu), gnomAD 10-18140785-G-T, REVEL 0.22, CADD 22.50
- V17M (p.Val17Met), gnomAD 10-18140785-G-A, REVEL 0.28, CADD 22.90
- V17V (p.Val17Val), gnomAD 10-18140787-G-T, CADD 13.40
- A18T (p.Ala18Thr), Ensembl rs2030295878
- A18V (p.Ala18Val), rs786205788, ClinGen CA301887, ClinVar RCV000170883, TOPMed rs786205788, REVEL 0.32, CADD 22.60, Uncertain significance, not provided
- p.Ala18dup, rs764468808, gnomAD 10-18140786-T-TGG, CADD 21.00
- A18E (p.Ala18Glu), gnomAD 10-18140789-C-A, REVEL 0.36, CADD 20.10
- A18A (p.Ala18Ala), rs1444080173, gnomAD 10-18140790-G-A, CADD 15.10
- Q19H (p.Gln19His), NCI-TCGA TCGA novel, ExAC rs759289370, gnomAD rs759289370, REVEL 0.15, CADD 23.90, Variant assessed as somatic; moderate impact.
- Q19K (p.Gln19Lys), gnomAD 10-18140791-C-A, REVEL 0.11, CADD 22.80
- Q19R (p.Gln19Arg), gnomAD 10-18140792-A-G, REVEL 0.19, CADD 23.40
- E20D (p.Glu20Asp), rs1046365611, ClinGen CA203321551, ClinVar RCV004129693, TOPMed rs1046365611, REVEL 0.12, CADD 21.90, Uncertain significance, Cardiovascular phenotype
- E20K (p.Glu20Lys), gnomAD rs1422234805, REVEL 0.43, CADD 24.20
- E20Q (p.Glu20Gln), gnomAD rs1422234805, REVEL 0.30, CADD 23.70
- E20G (p.Glu20Gly), gnomAD 10-18140795-A-G, REVEL 0.42, CADD 24.00
- E20E (p.Glu20Glu), rs1046365611, gnomAD 10-18140796-G-A, CADD 14.20
- I21S (p.Ile21Ser), Ensembl rs549888828
- I21V (p.Ile21Val), gnomAD 10-18140797-A-G, REVEL 0.20, CADD 18.60
- I21I (p.Ile21Ile), gnomAD 10-18140799-C-A, CADD 13.80
- I21F (p.Ile21Phe), rs780943798, gnomAD 10-18141213-A-T, CADD 20.80
- I21N (p.Ile21Asn), gnomAD 10-18141214-T-A, CADD 20.30
- I21T (p.Ile21Thr), rs2030355651, gnomAD 10-18141214-T-C, CADD 20.70
- I21M (p.Ile21Met), rs2030355938, gnomAD 10-18141215-C-G, CADD 19.40
- Q22* (p.Gln22Ter), gnomAD rs1328545245, CADD 37.00
- Q22E (p.Gln22Glu), gnomAD rs1328545245, REVEL 0.10, CADD 18.50
- Q22H (p.Gln22His), Ensembl rs2030298081
- Q22R (p.Gln22Arg), TOPMed rs988658582, gnomAD rs988658582, REVEL 0.11, CADD 20.70
- Q22P (p.Gln22Pro), gnomAD 10-18140801-A-C, REVEL 0.13, CADD 16.70
- M23V (p.Met23Val), gnomAD 10-18140803-A-G, REVEL 0.25, CADD 23.60
- M23I (p.Met23Ile), gnomAD 10-18140805-G-A, REVEL 0.16, CADD 24.40
- E24K (p.Glu24Lys), gnomAD rs1444039882, REVEL 0.28, CADD 24.90
- E24* (p.Glu24Ter), gnomAD 10-18140806-G-T, CADD 42.00
- E24D (p.Glu24Asp), gnomAD 10-18140808-A-C, REVEL 0.22, CADD 9.73
- E24E (p.Glu24Glu), rs769270939, gnomAD 10-18140808-A-G, CADD 10.80
- L25R (p.Leu25Arg), gnomAD rs1244576900, REVEL 0.58, CADD 23.70
- L25V (p.Leu25Val), ExAC rs775097809, gnomAD rs775097809, REVEL 0.20, CADD 15.60
- L25L (p.Leu25Leu), rs775097809, gnomAD 10-18140809-C-T, CADD 14.10
- L7del (p.Leu7del), gnomAD 10-18141196-GACT-, CADD 19.30
- L25M (p.Leu25Met), gnomAD 10-18141198-C-A, CADD 19.30
- L25P (p.Leu25Pro), gnomAD 10-18141199-T-C, CADD 19.00
- L25Q (p.Leu25Gln), gnomAD 10-18141205-T-A, CADD 20.30
- L26P (p.Leu26Pro), Ensembl rs1002404994, REVEL 0.49, CADD 22.60
- L26I (p.Leu26Ile), gnomAD 10-18140812-C-A, REVEL 0.26, CADD 22.80
- L26L (p.Leu26Leu), rs1281960623, gnomAD 10-18140814-A-G, CADD 14.30
- E27D (p.Glu27Asp), ExAC rs762401616, TOPMed rs762401616, gnomAD rs762401616, REVEL 0.18, CADD 18.20
- E27Q (p.Glu27Gln), TOPMed rs2030299512, Uncertain significance, Cardiovascular phenotype
- E27* (p.Glu27Ter), gnomAD 10-18140815-G-T, CADD 39.00
- E27E (p.Glu27Glu), rs762401616, gnomAD 10-18140817-G-A, CADD 13.60
- N28K (p.Asn28Lys), ExAC rs763573123, TOPMed rs763573123, gnomAD rs763573123, REVEL 0.12, CADD 23.40, Likely benign
- N28S (p.Asn28Ser), NCI-TCGA TCGA novel, Ensembl rs2130978874, Variant assessed as somatic; moderate impact.
- N28N (p.Asn28Asn), rs763573123, gnomAD 10-18140820-C-T, CADD 14.20
- N28I (p.Asn28Ile), gnomAD 10-18141184-A-T, CADD 21.20
- V29L (p.Val29Leu), rs750972281, ExAC rs750972281, TOPMed rs750972281, gnomAD rs750972281, REVEL 0.12, CADD 19.10, Variant assessed as somatic; moderate impact.
- V29M (p.Val29Met), rs750972281, ExAC rs750972281, TOPMed rs750972281, gnomAD rs750972281, REVEL 0.12, CADD 21.90, Uncertain significance, Cardiovascular phenotype
- V29A (p.Val29Ala), gnomAD 10-18140822-T-C, REVEL 0.15, CADD 17.30
- V29V (p.Val29Val), rs758806288, gnomAD 10-18140823-G-A, CADD 13.30
- A30V (p.Ala30Val), gnomAD rs1351768521, REVEL 0.24, CADD 21.20
- A30S (p.Ala30Ser), gnomAD 10-18140824-G-T, REVEL 0.23, CADD 16.20
- A30T (p.Ala30Thr), gnomAD 10-18140824-G-A, REVEL 0.23, CADD 20.50
- A30A (p.Ala30Ala), gnomAD 10-18140826-T-C, CADD 14.50
- P31S (p.Pro31Ser), NCI-TCGA Cosmic COSV9999, cosmic curated COSV99992, ExAC rs766827150, TOPMed rs766827150, REVEL 0.21, CADD 19.30, Variant assessed as somatic; moderate impact.
- P31T (p.Pro31Thr), ExAC rs766827150, TOPMed rs766827150, gnomAD rs766827150, REVEL 0.23, CADD 20.40
- P31L (p.Pro31Leu), gnomAD 10-18140828-C-T, REVEL 0.26, CADD 23.00
- P31P (p.Pro31Pro), rs1192957611, gnomAD 10-18140829-C-T, CADD 15.50
- A32T (p.Ala32Thr), cosmic curated COSV56634, gnomAD rs1243958682, REVEL 0.29, CADD 22.50
- A32V (p.Ala32Val), gnomAD rs1461072321, REVEL 0.40, CADD 22.60
- A32S (p.Ala32Ser), gnomAD 10-18140830-G-T, REVEL 0.16, CADD 22.40
- A32A (p.Ala32Ala), rs1057522395, gnomAD 10-18140832-G-C, CADD 15.00
- G33A (p.Gly33Ala), Ensembl rs2030302052, REVEL 0.31, CADD 21.80
- G33W (p.Gly33Trp), gnomAD rs2030301853, REVEL 0.53, CADD 25.40
- G33V (p.Gly33Val), gnomAD 10-18140834-G-T, REVEL 0.50, CADD 23.60
- G33G (p.Gly33Gly), gnomAD 10-18140835-G-T, CADD 14.70
- G33R (p.Gly33Arg), rs1239721383, gnomAD 10-18141189-G-A, CADD 20.50
- G33E (p.Gly33Glu), gnomAD 10-18141190-G-A, CADD 17.80
- G33* (p.Gly33Ter), gnomAD 10-18141195-G-T, CADD 20.40
- A34E (p.Ala34Glu), ExAC rs755229434, TOPMed rs755229434, gnomAD rs755229434, REVEL 0.46, CADD 22.60
- A34S (p.Ala34Ser), rs754097169, ClinGen CA301875, cosmic curated COSV10608, ClinVar RCV000170878, REVEL 0.13, CADD 20.80, Uncertain significance, not provided
- A34V (p.Ala34Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A34G (p.Ala34Gly), gnomAD 10-18140831-C-CG, CADD 31.00
- A34T (p.Ala34Thr), gnomAD 10-18140836-G-A, REVEL 0.14, CADD 22.70
- A34A (p.Ala34Ala), gnomAD 10-18140838-G-A, CADD 15.20
- L35P (p.Leu35Pro), rs373263114, ClinGen CA236641, ClinVar RCV000171621, ClinVar RCV001803145, REVEL 0.56, CADD 22.80, Uncertain significance, not provided; Brugada syndrome 4
- L35V (p.Leu35Val), TOPMed rs1311945957
- L35F (p.Leu35Phe), gnomAD 10-18140839-C-T, REVEL 0.27, CADD 22.40
- L35I (p.Leu35Ile), gnomAD 10-18140839-C-A, REVEL 0.21, CADD 21.50
- L35H (p.Leu35His), gnomAD 10-18140840-T-A, REVEL 0.28, CADD 23.20
- L35L (p.Leu35Leu), gnomAD 10-18140841-C-T, CADD 13.30
- G36R (p.Gly36Arg), Ensembl rs2030303741, REVEL 0.36, CADD 25.50
- G36V (p.Gly36Val), TOPMed rs2030303948, REVEL 0.29, CADD 23.40
- G36* (p.Gly36Ter), gnomAD 10-18140842-G-T, CADD 42.00
- G36E (p.Gly36Glu), gnomAD 10-18140843-G-A, REVEL 0.30, CADD 22.80
- G36G (p.Gly36Gly), gnomAD 10-18140844-A-C, CADD 16.10
- A37D (p.Ala37Asp), TOPMed rs967518861, gnomAD rs967518861, REVEL 0.29, CADD 21.00
- A37T (p.Ala37Thr), rs1422197851, gnomAD rs1422197851, REVEL 0.21, CADD 22.30, Variant assessed as somatic; moderate impact.
- A37P (p.Ala37Pro), gnomAD 10-18140845-G-C, REVEL 0.33, CADD 23.00
- A37S (p.Ala37Ser), gnomAD 10-18140845-G-T, REVEL 0.18, CADD 20.60
Public CACNB2 analysis runs
- CACNB2 analysis run — CACNB2 (1,243 variants) — completed 2026-08-20