CACNA1A (O00555) variants and mutations
CACNA1A (also known as O00555) is a human protein-coding gene encoding a voltage-dependent P/Q-type calcium channel subunit alpha-1A protein. Its P/Q-type calcium current is a major trigger for neurotransmitter release at central synapses and is especially important in cerebellar circuits. Pathogenic variants cause a spectrum including familial hemiplegic migraine, episodic ataxia, spinocerebellar ataxia type 6, epilepsy, and developmental disorders. This analysis covers 4,079 CACNA1A variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes Familial paroxysmal ataxia, episodic ataxia type 2, and migraine, familial hemiplegic, 1. Example CACNA1A variants include A2S, A2V, and R3C.
Variant analysis overview
- Gene: CACNA1A
- Protein: O00555
- UniProt accession: O00555
- Organism: Homo sapiens
- Variants analyzed: 4079
- Variant scope: all variants
- Completed: 2026-08-09
Variant and mutation evidence
- Variant composition: 3,597 unspecified-consequence records; 1 stop retained variant; 111 synonymous variants; 16 stop-gained variants; 302 missense variants; 13 in-frame deletions; 35 frameshift variants; 2 in-frame insertions; 2 substitution
- Prediction scores: 3,506 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Familial paroxysmal ataxia, episodic ataxia type 2, migraine, familial hemiplegic, 1, developmental and epileptic encephalopathy, 42, spinocerebellar ataxia type 6, Seizure, familial or sporadic hemiplegic migraine, epilepsy, neuropathic pain, fibromyalgia, restless legs syndrome, anxiety disorder.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 3 binding sites; 16 post-translational modification sites.
- Structural context: 512 variants have structural context.
- PTM context: 20 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, ClinGen, MaveDB, LitVar.
Notable CACNA1A variants
Examples include A2S, A2V, R3C, R3G, R3H, G5V, D6E, E7K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), rs2145193160, ClinGen CA404971402, ClinVar RCV002007885, Ensembl rs2145193160, REVEL 0.59, MetaLR 0.93, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- A2V (p.Ala2Val), rs927310190, ClinGen CA16620804, ClinVar RCV001362235, ClinVar RCV001704643, REVEL 0.61, MetaLR 0.89, Conflicting interpretations, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; Inborn g
- R3C (p.Arg3Cys), rs1326606155, ClinGen CA404971397, ClinVar RCV001886924, ClinVar RCV006272465, REVEL 0.73, AlphaMissense 0.80, Uncertain significance, not provided; Episodic ataxia type 2; Developmental and epileptic encephalopathy
- R3G (p.Arg3Gly), rs1326606155, ClinGen CA404971399, ClinVar RCV002041976, TOPMed rs1326606155, AlphaMissense 0.80, MetaLR 0.95, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R3H (p.Arg3His), rs2513710483, ClinGen CA404971394, ClinVar RCV003793275, REVEL 0.75, MetaLR 0.95, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- G5V (p.Gly5Val), gnomAD rs1300034585, REVEL 0.55, MetaLR 0.83
- D6E (p.Asp6Glu), cosmic curated COSV64189, REVEL 0.21, MetaLR 0.67
- E7K (p.Glu7Lys), rs2513710370, ClinGen CA404971371, ClinVar RCV003797614, REVEL 0.53, MetaLR 0.87, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- M8I (p.Met8Ile), Ensembl rs1983019847, REVEL 0.31, MetaLR 0.70
- M8T (p.Met8Thr), cosmic curated COSV10080, REVEL 0.35, MetaLR 0.74
- P9L (p.Pro9Leu), rs1487101039, ClinGen CA404971351, cosmic curated COSV64196, ClinVar RCV001988476, REVEL 0.59, AlphaMissense 0.67, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not spec
- P9R (p.Pro9Arg), rs1487101039, ClinGen CA404971350, ClinVar RCV003800047, AlphaMissense 0.67, MetaLR 0.91, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- P9S (p.Pro9Ser), rs1555797187, ClinGen CA404971352, ClinVar RCV002710629, ClinVar RCV005639431, REVEL 0.42, MetaLR 0.87, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; not prov
- A10S (p.Ala10Ser), TOPMed rs1326483165, gnomAD rs1326483165, REVEL 0.23, MetaLR 0.61, Uncertain significance, not provided
- A10V (p.Ala10Val), rs952757731, ClinGen CA16620803, ClinVar RCV000481875, ClinVar RCV000697164, REVEL 0.25, MetaLR 0.70, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; Inborn g
- R11C (p.Arg11Cys), rs2513710289, ClinGen CA404971341, ClinVar RCV003018036, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R11H (p.Arg11His), ExAC rs762592657, gnomAD rs762592657, REVEL 0.60, MetaLR 0.90
- Y12C (p.Tyr12Cys), rs994265107, ClinGen CA305562806, ClinVar RCV001229380, ClinVar RCV003145434, REVEL 0.56, MetaLR 0.92, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not spec
- Y12F (p.Tyr12Phe), rs994265107, ClinGen CA404971335, ClinVar RCV001665178, ClinVar RCV003771814, REVEL 0.53, MetaLR 0.91, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not prov
- Y12H (p.Tyr12His), rs1983017662, ClinGen CA404971338, ClinVar RCV002289278, ClinVar RCV003097775, AlphaMissense 0.91, MetaLR 0.91, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- G13A (p.Gly13Ala), rs1462714993, ClinGen CA404971327, ClinVar RCV001264642, gnomAD rs1462714993, AlphaMissense 0.93, MetaLR 0.93, Likely benign, Neurodevelopmental abnormality
- G13E (p.Gly13Glu), gnomAD rs1462714993, Likely benign
- G13R (p.Gly13Arg), rs1202097056, ClinGen CA404971330, ClinVar RCV003149297, ClinGen CA404971331, REVEL 0.62, MetaLR 0.94, Uncertain significance, not provided
- G14E (p.Gly14Glu), cosmic curated COSV10466, TOPMed rs1383227916, gnomAD rs1383227916, REVEL 0.63, MetaLR 0.90
- G14R (p.Gly14Arg), cosmic curated COSV10527, Ensembl rs2145192995, REVEL 0.68, MetaLR 0.92
- G15R (p.Gly15Arg), rs2513710149, ClinGen CA404971319, ClinVar RCV002461831, REVEL 0.56, MetaLR 0.92, Uncertain significance, not provided
- S17C (p.Ser17Cys), rs931963287, ClinGen CA404971303, ClinVar RCV001244508, ClinVar RCV001586086, AlphaMissense 0.36, MetaLR 0.73, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not prov
- S17F (p.Ser17Phe), TOPMed rs931963287, REVEL 0.36, AlphaMissense 0.36, Uncertain significance, not provided
- S17P (p.Ser17Pro), Ensembl rs2145192972, REVEL 0.28, MetaLR 0.55
- G18R (p.Gly18Arg), TOPMed rs1434963414, gnomAD rs1434963414
- G18W (p.Gly18Trp), TOPMed rs1434963414, gnomAD rs1434963414, REVEL 0.63, MetaLR 0.89
- A19E (p.Ala19Glu), rs764604964, ClinGen CA404971294, ClinVar RCV002942047, cosmic curated COSV64203, REVEL 0.26, MetaLR 0.55, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- A19T (p.Ala19Thr), rs923359230, ClinGen CA16043075, ClinVar RCV001350900, ClinVar RCV001726154, REVEL 0.24, MetaLR 0.60, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not prov
- A19V (p.Ala19Val), ExAC rs764604964, gnomAD rs764604964, REVEL 0.27, MetaLR 0.59
- A20V (p.Ala20Val), rs2513710012, ClinGen CA404971287, ClinVar RCV003052244, REVEL 0.25, MetaLR 0.66, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- A21T (p.Ala21Thr), cosmic curated COSV64215, REVEL 0.36, MetaLR 0.78
- A21V (p.Ala21Val), rs15999, ClinGen CA9241108, ClinVar RCV000444099, ClinVar RCV000542201, REVEL 0.37, MetaLR 0.80, Benign, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not spec
- G22A (p.Gly22Ala), rs1983011989, ClinGen CA404971277, ClinVar RCV002036635, Ensembl rs1983011989, AlphaMissense 0.70, MetaLR 0.81, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- G22E (p.Gly22Glu), rs1983011989, ClinGen CA404971278, ClinVar RCV001892122, ClinVar RCV004785359, AlphaMissense 0.70, MetaLR 0.81, Uncertain significance, not provided; Episodic ataxia type 2; Developmental and epileptic encephalopathy
- G22R (p.Gly22Arg), rs2513709975, ClinGen CA404971279, ClinVar RCV003034315, cosmic curated COSV64190, REVEL 0.47, MetaLR 0.79, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- G22W (p.Gly22Trp), cosmic curated COSV64193, REVEL 0.55, MetaLR 0.84
- V23G (p.Val23Gly), Ensembl rs569659187, MetaLR 0.60, MetaSVM -0.26
- V23A (p.Val23Ala), rs952757731, Uncertain significance
- V25G (p.Val25Gly), rs565157998, ClinGen CA9241106, ClinVar RCV001071758, 1000Genomes rs565157998, REVEL 0.35, MetaLR 0.71, Likely benign, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- V25L (p.Val25Leu), cosmic curated COSV64214
- G26C (p.Gly26Cys), rs2513709916, ClinGen CA404971257, ClinVar RCV002746222, REVEL 0.63, MetaLR 0.86, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- S27G (p.Ser27Gly), rs1230511962, ClinGen CA404971252, ClinVar RCV003787642, ClinVar RCV006276408, REVEL 0.27, MetaLR 0.62, Uncertain significance, Inborn genetic diseases; Episodic ataxia type 2; Developmental and epileptic enc
- S27I (p.Ser27Ile), rs1349415232, ClinGen CA404971248, ClinVar RCV003784667, TOPMed rs1349415232, REVEL 0.41, MetaLR 0.68, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- S27T (p.Ser27Thr), TOPMed rs1349415232, gnomAD rs1349415232, MetaLR 0.68, MetaSVM -0.14, Uncertain significance
- G28R (p.Gly28Arg), cosmic curated COSV64208, REVEL 0.39, MetaLR 0.77
- G30R (p.Gly30Arg), ExAC rs774608710, gnomAD rs774608710, Uncertain significance, not provided
- G30W (p.Gly30Trp), ExAC rs774608710, gnomAD rs774608710, REVEL 0.47, MetaLR 0.89
- R31* (p.Arg31Ter), rs2513709839, ClinGen CA404971227, ClinVar RCV003336697, Pathogenic
- A33S (p.Ala33Ser), rs749474997, ClinGen CA9241102, cosmic curated COSV64210, ClinVar RCV002025881, REVEL 0.31, MetaLR 0.83, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- A33T (p.Ala33Thr), cosmic curated COSV10466, REVEL 0.32, MetaLR 0.85
- G34E (p.Gly34Glu), rs1396213397, ClinGen CA404971209, ClinVar RCV002886176, gnomAD rs1396213397, REVEL 0.57, MetaLR 0.87, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- G34R (p.Gly34Arg), rs1402827595, ClinGen CA404971211, ClinVar RCV003799570, ClinVar RCV004736402, REVEL 0.58, MetaLR 0.88, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- G35D (p.Gly35Asp), ExAC rs756090706, gnomAD rs756090706, REVEL 0.47, MetaLR 0.90
- S36G (p.Ser36Gly), rs2513709713, ClinGen CA404971200, ClinVar RCV003329581, REVEL 0.25, MetaLR 0.60, Uncertain significance, not provided
- R37G (p.Arg37Gly), rs780987148, ClinGen CA404971193, ClinVar RCV001767299, ExAC rs780987148, REVEL 0.30, MetaLR 0.76, Uncertain significance, not provided
- R37Q (p.Arg37Gln), rs1391039223, ClinGen CA404971192, cosmic curated COSV10080, ClinVar RCV003068457, REVEL 0.46, MetaLR 0.80, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- R37W (p.Arg37Trp), cosmic curated COSV10592, ExAC rs780987148, gnomAD rs780987148, REVEL 0.42, MetaLR 0.83, Uncertain significance
- G39D (p.Gly39Asp), rs990248774, ClinGen CA305562729, cosmic curated COSV64191, ClinVar RCV003129188, AlphaMissense 0.83, MetaLR 0.94, Uncertain significance, not provided
- G40R (p.Gly40Arg), TOPMed rs1240542236, gnomAD rs1240542236, REVEL 0.56, MetaLR 0.84
- G40W (p.Gly40Trp), cosmic curated COSV10080, TOPMed rs1240542236, gnomAD rs1240542236, REVEL 0.67, MetaLR 0.91
- Q41L (p.Gln41Leu), ExAC rs751376977, TOPMed rs751376977, gnomAD rs751376977, REVEL 0.36, MetaLR 0.68, Uncertain significance, not provided
- P42S (p.Pro42Ser), rs2145192584, ClinGen CA404971161, ClinVar RCV002260779, ClinVar RCV003147744, AlphaMissense 0.34, MetaLR 0.85, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not prov
- G43R (p.Gly43Arg), ExAC rs763931319, TOPMed rs763931319, gnomAD rs763931319, REVEL 0.57, MetaLR 0.92
- A44E (p.Ala44Glu), cosmic curated COSV64205, REVEL 0.35, MetaLR 0.76
- A44G (p.Ala44Gly), gnomAD rs1280455908, REVEL 0.30, MetaLR 0.60
- A44T (p.Ala44Thr), rs201398669, ClinGen CA9241093, ClinVar RCV002049964, ClinVar RCV002478081, REVEL 0.28, MetaLR 0.67, Conflicting interpretations, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; Spinocer
- A44V (p.Ala44Val), cosmic curated COSV64199, REVEL 0.33, MetaLR 0.75
- R46K (p.Arg46Lys), cosmic curated COSV10080, MetaLR 0.76, MetaSVM 0.21
- M47I (p.Met47Ile), TOPMed rs1225124202, gnomAD rs1225124202, REVEL 0.30, MetaLR 0.74, Uncertain significance, not provided
- M47K (p.Met47Lys), rs2513709336, ClinGen CA404971129, ClinVar RCV003802736, REVEL 0.50, MetaLR 0.75, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- K49* (p.Lys49Ter), cosmic curated COSV10080
- Q50L (p.Gln50Leu), cosmic curated COSV10080, MetaLR 0.82, MetaSVM 0.49
- S51* (p.Ser51Ter), cosmic curated COSV64189
- M52T (p.Met52Thr), rs2513709279, ClinGen CA404971090, ClinVar RCV003318195, ClinVar RCV004963612, REVEL 0.57, MetaLR 0.75, Uncertain significance, not provided; Inborn genetic diseases
- M52V (p.Met52Val), rs758952079, ClinGen CA9241091, ClinVar RCV002681850, ExAC rs758952079, REVEL 0.52, MetaLR 0.70, Likely benign, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- A53T (p.Ala53Thr), rs2513709272, ClinGen CA404971083, ClinVar RCV003051835, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- A53V (p.Ala53Val), cosmic curated COSV64201, REVEL 0.84, MetaLR 0.94, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; not prov
- Q54* (p.Gln54Ter), cosmic curated COSV10592
- Q54H (p.Gln54His), cosmic curated COSV64191, cosmic curated COSV10080, Uncertain significance, not provided; Developmental and epileptic encephalopathy, 42; Episodic ataxia ty
- A56G (p.Ala56Gly), rs2513709203, ClinGen CA404971060, ClinVar RCV003800411, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R57Q (p.Arg57Gln), rs2513709171, ClinGen CA404971055, ClinVar RCV003800645, cosmic curated COSV64194, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R57W (p.Arg57Trp), rs1982997781, ClinGen CA404971057, cosmic curated COSV64216, ClinVar RCV001320428, AlphaMissense 1.00, MetaLR 0.95, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- T58I (p.Thr58Ile), cosmic curated COSV64197, MetaLR 0.93, MetaSVM 1.05
- M59T (p.Met59Thr), rs2513709081, ClinGen CA404971043, ClinVar RCV003143876, Uncertain significance, not provided
- M59V (p.Met59Val), rs1599396496, ClinGen CA404971045, ClinVar RCV000790469, Ensembl rs1599396496, AlphaMissense 0.92, MetaLR 0.86, Uncertain significance, Developmental and epileptic encephalopathy, 42
- A60T (p.Ala60Thr), cosmic curated COSV64214
- A60V (p.Ala60Val), cosmic curated COSV64190, MetaLR 0.93, MetaSVM 1.06
- L61P (p.Leu61Pro), rs2513709063, ClinGen CA404971028, ClinVar RCV003333573, Uncertain significance, Episodic ataxia type 2
- Y62C (p.Tyr62Cys), rs2513709034, ClinGen CA404971022, ClinVar RCV003233020, ClinVar RCV003779849, Pathogenic/Likely pathogenic, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; Focal ep
- Y62H (p.Tyr62His), rs2513709042, ClinGen CA404971025, ClinVar RCV002801531, ClinVar RCV006254342, Likely pathogenic, Migraine, familial hemiplegic, 1; Episodic ataxia type 2; Developmental and epil
- Y62N (p.Tyr62Asn), rs2513709042, ClinGen CA404971026, ClinVar RCV002853067, Likely pathogenic, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- P64H (p.Pro64His), rs2145192387, ClinGen CA404971007, ClinVar RCV001507937, Ensembl rs2145192387, AlphaMissense 1.00, MetaLR 0.94, Uncertain significance, not provided
- P64L (p.Pro64Leu), rs2145192387, ClinGen CA404971005, ClinVar RCV001365794, Ensembl rs2145192387, AlphaMissense 1.00, MetaLR 0.94, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- P64S (p.Pro64Ser), rs1982996175, ClinGen CA404971008, ClinVar RCV001253517, Ensembl rs1982996175, AlphaMissense 1.00, MetaLR 0.94, Uncertain significance, Developmental and epileptic encephalopathy, 42
- P66R (p.Pro66Arg), Ensembl rs1982995548, REVEL 0.90, MetaLR 0.93
- V67I (p.Val67Ile), rs1982994821, ClinGen CA404970991, cosmic curated COSV10889, ClinVar RCV003793658, AlphaMissense 0.53, MetaLR 0.15, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R68* (p.Arg68Ter), rs2513708889, ClinGen CA404970984, ClinVar RCV002467206, Pathogenic
- R68L (p.Arg68Leu), rs576099495, ClinGen CA404970983, ClinVar RCV003333361, AlphaMissense 0.84, MetaLR 0.12, Likely pathogenic, Episodic ataxia type 2
- R68P (p.Arg68Pro), cosmic curated COSV10969, MetaLR 0.19, MetaSVM -0.66
- R68Q (p.Arg68Gln), rs576099495, ClinGen CA9241087, cosmic curated COSV64197, ClinVar RCV001312855, REVEL 0.12, AlphaMissense 0.84, Conflicting interpretations, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2; not prov
- N70S (p.Asn70Ser), rs749526415, ClinGen CA9241086, ClinVar RCV001901839, ClinVar RCV002422915, REVEL 0.12, MetaLR 0.10, Conflicting interpretations, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; Inborn g
- C71Y (p.Cys71Tyr), Ensembl rs1982993575, MetaLR 0.35, MetaSVM -0.22
- L72F (p.Leu72Phe), ExAC rs775562753, TOPMed rs775562753, gnomAD rs775562753, REVEL 0.06, MetaLR 0.04
- L72H (p.Leu72His), cosmic curated COSV64191
- T73M (p.Thr73Met), gnomAD rs1472719188, REVEL 0.44, MetaLR 0.38
- V74L (p.Val74Leu), gnomAD rs1190000582, REVEL 0.17, MetaLR 0.29
- N75I (p.Asn75Ile), cosmic curated COSV10080, MetaLR 0.36, MetaSVM -0.22
- N75K (p.Asn75Lys), rs1982991598, ClinGen CA404970934, ClinVar RCV001235855, Ensembl rs1982991598, CADD 4.27, SIFT 0.19, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- R76L (p.Arg76Leu), cosmic curated COSV10442, MetaLR 0.37, MetaSVM -0.30
- R76W (p.Arg76Trp), cosmic curated COSV64195, gnomAD rs1469683674, REVEL 0.43, MetaLR 0.28
- F79V (p.Phe79Val), rs2145192231, ClinGen CA404970914, ClinVar RCV001897424, Ensembl rs2145192231, AlphaMissense 1.00, MetaLR 0.53, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- F79Y (p.Phe79Tyr), gnomAD rs1982990307, REVEL 0.41, MetaLR 0.37
- E83K (p.Glu83Lys), cosmic curated COSV10527
- D84H (p.Asp84His), gnomAD rs1215332070
- N85I (p.Asn85Ile), ExAC rs746902081, gnomAD rs746902081, REVEL 0.76, MetaLR 0.64, Likely benign
- N85S (p.Asn85Ser), rs746902081, ClinGen CA404970867, ClinVar RCV001063128, ExAC rs746902081, REVEL 0.59, MetaLR 0.54, Likely benign, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- V86L (p.Val86Leu), gnomAD rs1205659362, REVEL 0.05, MetaLR 0.20
- V86M (p.Val86Met), cosmic curated COSV64199, REVEL 0.09, MetaLR 0.25
- V87M (p.Val87Met), TOPMed rs1982987763
- R88S (p.Arg88Ser), rs2513708594, ClinGen CA404970846, ClinVar RCV003985593, Uncertain significance, CACNA1A-related disorder
- K89R (p.Lys89Arg), TOPMed rs1355490857, gnomAD rs1355490857, REVEL 0.15, MetaLR 0.11
- Y90H (p.Tyr90His), cosmic curated COSV10651
- A91P (p.Ala91Pro), rs2513708571, ClinGen CA404970827, ClinVar RCV003985592, Uncertain significance, CACNA1A-related disorder
- A91T (p.Ala91Thr), cosmic curated COSV64195, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- K93M (p.Lys93Met), TOPMed rs1982986172, MetaLR 0.32, MetaSVM -0.75
- T95S (p.Thr95Ser), rs2513708544, ClinGen CA404970795, ClinVar RCV002834473, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- E96* (p.Glu96Ter), rs2513708527, ClinGen CA404970791, ClinVar RCV003805033, Pathogenic
- E96K (p.Glu96Lys), cosmic curated COSV64197
- W97* (p.Trp97Ter), cosmic curated COSV10889
- P98L (p.Pro98Leu), rs2145192098, ClinGen CA404970772, ClinVar RCV002048563, Ensembl rs2145192098, AlphaMissense 0.90, MetaLR 0.41, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- P98S (p.Pro98Ser), ExAC rs752452147, gnomAD rs752452147, REVEL 0.30, MetaLR 0.33
- P99H (p.Pro99His), cosmic curated COSV10080, REVEL 0.83, MetaLR 0.75
- P99L (p.Pro99Leu), cosmic curated COSV10527, ExAC rs763303899, gnomAD rs763303899, REVEL 0.69, MetaLR 0.67
- E101A (p.Glu101Ala), rs2060985088, ClinGen CA404967956, ClinVar RCV001288837, Ensembl rs2060985088, AlphaMissense 0.94, MetaLR 0.64, Uncertain significance, not provided
- E101K (p.Glu101Lys), rs886037944, ClinGen CA404967957, ClinVar RCV001544846, ClinVar RCV001882616, AlphaMissense 0.86, MetaLR 0.66, Likely pathogenic, not provided; Developmental and epileptic encephalopathy, 42; Episodic ataxia ty
- E101Q (p.Glu101Gln), rs886037944, ClinGen CA10586393, ClinVar RCV000240952, UniProt VAR 077071, AlphaMissense 0.86, MetaLR 0.66, Pathogenic, Developmental and epileptic encephalopathy, 42
- M103I (p.Met103Ile), cosmic curated COSV64202, Ensembl rs867125827, MetaLR 0.15, MetaSVM -0.93
- M103T (p.Met103Thr), rs2060984965, ClinGen CA404967939, ClinVar RCV002325791, TOPMed rs2060984965, REVEL 0.40, MetaLR 0.27, Uncertain significance, Inborn genetic diseases
- L105V (p.Leu105Val), cosmic curated COSV64191
- A106T (p.Ala106Thr), cosmic curated COSV10080, Ensembl rs960396840, REVEL 0.16, MetaLR 0.15
- A106V (p.Ala106Val), rs761374169, ClinVar RCV004592221, TOPMed rs761374169, REVEL 0.18, MetaLR 0.15, Uncertain significance, not provided
- I108M (p.Ile108Met), rs2144947382, ClinGen CA404967904, ClinVar RCV001361329, Ensembl rs2144947382, AlphaMissense 0.93, MetaLR 0.62, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- I108T (p.Ile108Thr), rs2513512273, ClinGen CA404967906, ClinVar RCV003035069, Likely pathogenic, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- I108V (p.Ile108Val), rs1599294284, ClinGen CA404967909, ClinVar RCV000793236, ClinVar RCV001089748, AlphaMissense 0.48, MetaLR 0.55, Conflicting interpretations, Developmental and epileptic encephalopathy, 42; not provided; Episodic ataxia ty
- A110V (p.Ala110Val), rs1085307798, ClinGen CA404967891, cosmic curated COSV64203, ClinVar RCV000489790, REVEL 0.39, MetaLR 0.37, Uncertain significance, not provided
- N111S (p.Asn111Ser), cosmic curated COSV64193, MetaLR 0.62, MetaSVM 0.31
- I113F (p.Ile113Phe), rs746955115, ClinGen CA404967873, ClinVar RCV002581906, REVEL 0.51, MetaLR 0.38, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- I113V (p.Ile113Val), rs746955115, ClinGen CA9241061, ClinVar RCV001308789, ClinVar RCV001773618, REVEL 0.16, MetaLR 0.06, Uncertain significance, not provided; Developmental and epileptic encephalopathy, 42; Episodic ataxia ty
- V114I (p.Val114Ile), cosmic curated COSV64202, REVEL 0.45, MetaLR 0.55, Uncertain significance, not provided
- L115F (p.Leu115Phe), cosmic curated COSV64194
- A116S (p.Ala116Ser), ExAC rs778725158, TOPMed rs778725158, gnomAD rs778725158, REVEL 0.61, MetaLR 0.61, Uncertain significance, not provided
- A116T (p.Ala116Thr), rs778725158, ClinGen CA404967855, ClinVar RCV000653328, ExAC rs778725158, REVEL 0.63, MetaLR 0.52, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- A116V (p.Ala116Val), gnomAD rs1309534312, REVEL 0.73, MetaLR 0.65
- E118D (p.Glu118Asp), rs2144947250, ClinGen CA404967840, ClinVar RCV002263151, Ensembl rs2144947250, AlphaMissense 1.00, MetaLR 0.51, Uncertain significance, not provided
- E118K (p.Glu118Lys), cosmic curated COSV10466
- Q119* (p.Gln119Ter), cosmic curated COSV64194
- L121V (p.Leu121Val), cosmic curated COSV10080
- P122L (p.Pro122Leu), Ensembl rs2144947210, MetaLR 0.75, MetaSVM 0.68
- D123N (p.Asp123Asn), rs753467037, ClinGen CA9241055, ClinVar RCV001889698, ClinVar RCV003985529, REVEL 0.09, MetaLR 0.14, Conflicting interpretations, CACNA1A-related disorder; not provided; Episodic ataxia type 2
- D123V (p.Asp123Val), rs1555789420, ClinGen CA404967807, ClinVar RCV000660501, ClinVar RCV006556501, AlphaMissense 0.33, MetaLR 0.13, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- D124E (p.Asp124Glu), rs1342963547, ClinGen CA404967797, ClinVar RCV003238962, ClinVar RCV005794512, REVEL 0.04, MetaLR 0.06, Uncertain significance, not provided; Inborn genetic diseases
- D124G (p.Asp124Gly), rs2513512080, ClinGen CA404967800, ClinVar RCV003374692, Uncertain significance, Inborn genetic diseases
- K126E (p.Lys126Glu), Ensembl rs2060983445
- T127A (p.Thr127Ala), rs2144947148, ClinGen CA404967779, ClinVar RCV001927247, ClinVar RCV005792196, AlphaMissense 0.91, MetaLR 0.36, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; Inborn g
- T127N (p.Thr127Asn), cosmic curated COSV64209, MetaLR 0.28, MetaSVM -0.51
- P128L (p.Pro128Leu), rs779447041, ClinGen CA9241054, ClinVar RCV003809869, ExAC rs779447041, REVEL 0.61, MetaLR 0.69, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42
- P128S (p.Pro128Ser), cosmic curated COSV64200, TOPMed rs2060983382, REVEL 0.60, MetaLR 0.67
- R132Q (p.Arg132Gln), rs764554276, ClinGen CA9241051, cosmic curated COSV64207, ClinVar RCV002791719, REVEL 0.70, MetaLR 0.93, Uncertain significance, Developmental and epileptic encephalopathy, 42; Episodic ataxia type 2
- R132W (p.Arg132Trp), rs2513511988, ClinGen CA404967745, ClinVar RCV003808345, ClinVar RCV004736406, REVEL 0.69, MetaLR 0.93, Uncertain significance, Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42; not prov
- E137K (p.Glu137Lys), rs1057518116, ClinGen CA16043080, cosmic curated COSV64207, ClinVar RCV000413159, AlphaMissense 0.99, MetaLR 0.97, Likely pathogenic, not provided
- Y139C (p.Tyr139Cys), cosmic curated COSV64191, MetaLR 0.96, MetaSVM 1.10
- F140L (p.Phe140Leu), TOPMed rs1168776627, MetaLR 0.97, MetaSVM 1.09
- I141T (p.Ile141Thr), rs2144936441, ClinGen CA404967670, ClinVar RCV002214096, ClinVar RCV004785531, AlphaMissense 0.94, MetaLR 0.77, Uncertain significance, not provided; CACNA1A-related complex neurodevelopmental disorder
- G142E (p.Gly142Glu), cosmic curated COSV10080
- G142R (p.Gly142Arg), cosmic curated COSV10080, Ensembl rs2060943071
Public CACNA1A analysis runs
- CACNA1A analysis run — CACNA1A (4,079 variants) — completed 2026-08-09