CDKL5 (Cyclin-dependent kinase-like 5) variants and mutations
CDKL5 (also known as Cyclin-dependent kinase-like 5) is a human protein-coding gene encoding a cyclin-dependent kinase-like 5 protein. It phosphorylates neuronal substrates involved in synapse development, cytoskeletal organization, and signaling during early brain maturation. Loss-of-function variants cause CDKL5 deficiency disorder with very early epilepsy and severe developmental impairment. This analysis covers 1,181 CDKL5 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes developmental and epileptic encephalopathy, 2, CDKL5 disorder, and Angelman syndrome. Example CDKL5 variants include K2R, K2K, and I3F.
Variant analysis overview
- Gene: CDKL5
- Protein: Cyclin-dependent kinase-like 5
- UniProt accession: O76039
- Organism: Homo sapiens
- Variants analyzed: 1181
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,041 unspecified-consequence records; 4 natural variant; 65 missense variants; 51 synonymous variants; 5 frameshift variants; 4 splice-region variants; 6 stop-gained variants; 5 substitution
- Prediction scores: 958 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental and epileptic encephalopathy, 2, CDKL5 disorder, Angelman syndrome, atypical Rett syndrome, X-linked retinoschisis, infantile spasms, Retinal dystrophy, hereditary disease, Rett syndrome, Epileptic encephalopathy, retinoschisis, Seizure.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 4 post-translational modification sites.
- Structural context: 465 variants have structural context.
- PTM context: 4 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 CDKL5 variants
Examples include K2R, K2K, I3F, I3I, P4L, N5D, I6T, I6V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K2R (p.Lys2Arg), gnomAD X-18507101-A-G, MetaLR 0.32, MetaSVM -0.19
- K2K (p.Lys2Lys), gnomAD X-18507102-G-A, CADD 12.60
- I3F (p.Ile3Phe), rs138539908, ClinGen CA10360168, ClinVar RCV000460307, 1000Genomes rs138539908, MetaLR 0.39, MetaSVM -0.20, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- I3I (p.Ile3Ile), gnomAD X-18507105-T-C, CADD 13.30
- P4L (p.Pro4Leu), gnomAD X-18507107-C-T, MetaLR 0.40, MetaSVM -0.13
- N5D (p.Asn5Asp), rs767844474, ClinGen CA10360169, ClinVar RCV000482464, ClinVar RCV002526606, MetaLR 0.14, MetaSVM -0.91, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like; not provi
- I6T (p.Ile6Thr), rs746036179, ClinGen CA10360170, cosmic curated COSV10749, ClinVar RCV002900452, MetaLR 0.23, MetaSVM -0.48, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- I6V (p.Ile6Val), rs1922604127, ClinGen CA412489510, ClinVar RCV003781379, TOPMed rs1922604127, AlphaMissense 0.06, MetaLR 0.14, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- I6N (p.Ile6Asn), rs1458838945, gnomAD X-18507111-C-CA, CADD 25.30
- I6I (p.Ile6Ile), gnomAD X-18507114-T-C, CADD 13.10
- G7A (p.Gly7Ala), gnomAD rs1922604717, MetaLR 0.26, MetaSVM -0.48
- G7C (p.Gly7Cys), cosmic curated COSV10118, MetaLR 0.46, MetaSVM -0.13
- G7G (p.Gly7Gly), rs1922604912, gnomAD X-18507117-T-C, CADD 13.30
- N8D (p.Asn8Asp), gnomAD rs1389285694, MetaLR 0.11, MetaSVM -0.75
- N8N (p.Asn8Asn), rs1465523714, gnomAD X-18507120-T-C, CADD 12.60
- V9A (p.Val9Ala), rs1569197962, ClinGen CA412489533, ClinVar RCV000688793, Ensembl rs1569197962, MetaLR 0.21, MetaSVM -0.69, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- M10T (p.Met10Thr), rs2518776860, ClinGen CA412489539, ClinVar RCV003228263, Uncertain significance, not provided
- K12E (p.Lys12Glu), cosmic curated COSV66110
- K12T (p.Lys12Thr), NCI-TCGA Cosmic COSV6611, cosmic curated COSV66110, MetaLR 0.13, MetaSVM -0.94, Variant assessed as somatic; moderate impact.
- F13I (p.Phe13Ile), rs2147092100, ClinGen CA412489560, ClinVar RCV001823439, Ensembl rs2147092100, AlphaMissense 1.00, MetaLR 0.38, Uncertain significance, Developmental and epileptic encephalopathy, 2
- F13S (p.Phe13Ser), rs1922605766, ClinGen CA412489564, ClinVar RCV001194616, ClinVar RCV001204295, AlphaMissense 1.00, MetaLR 0.41, Likely pathogenic, CDKL5 disorder
- F13L (p.Phe13Leu), gnomAD X-18507135-T-G, MetaLR 0.31, MetaSVM -0.38
- E14E (p.Glu14Glu), rs1300830629, gnomAD X-18507138-G-A, CADD 10.90
- I15V (p.Ile15Val), gnomAD X-18507139-A-G, MetaLR 0.06, MetaSVM -1.04
- L16V (p.Leu16Val), rs2518776882, ClinGen CA412489584, ClinVar RCV003314366, Uncertain significance, Developmental and epileptic encephalopathy, 2
- L16I (p.Leu16Ile), gnomAD X-18507142-C-A, MetaLR 0.15, MetaSVM -0.84
- G17R (p.Gly17Arg), cosmic curated COSV10532, MetaLR 0.17, MetaSVM -0.75
- G17G (p.Gly17Gly), rs772299455, gnomAD X-18507147-G-A, CADD 12.10
- V18D (p.Val18Asp), rs1602230515, ClinGen CA412489598, ClinVar RCV000816804, ClinVar RCV005902063, AlphaMissense 0.99, MetaLR 0.37, Pathogenic, Angelman syndrome-like; Developmental and epileptic encephalopathy, 2
- V19I (p.Val19Ile), gnomAD X-18507151-G-A, MetaLR 0.10, MetaSVM -0.89
- V19V (p.Val19Val), gnomAD X-18507153-A-G, CADD 12.50
- G20D (p.Gly20Asp), rs786204962, ClinGen CA235605, ClinVar RCV000169987, ClinVar RCV001850412, AlphaMissense 1.00, MetaLR 0.83, Likely pathogenic, CDKL5 disorder; Developmental and epileptic encephalopathy, 2; Angelman syndrome
- G20R (p.Gly20Arg), rs267608418, ClinGen CA170496, ClinVar RCV000133379, ClinVar RCV002515935, AlphaMissense 1.00, MetaLR 0.74, Pathogenic
- G20S (p.Gly20Ser), rs267608418, ClinGen CA412489608, ClinVar RCV001047599, ClinVar RCV005912483, AlphaMissense 1.00, MetaLR 0.74, Likely pathogenic, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- G20V (p.Gly20Val), rs786204962, ClinGen CA412489610, ClinVar RCV001507056, ClinVar RCV001819879, AlphaMissense 1.00, MetaLR 0.83, Pathogenic, CDKL5 disorder
- G20G (p.Gly20Gly), gnomAD X-18507156-T-C, CADD 13.00
- E21D (p.Glu21Asp), rs2518776916, ClinGen CA412489617, ClinVar RCV002809357, ClinVar RCV005932374, Uncertain significance, Inborn genetic diseases
- E21G (p.Glu21Gly), rs587783406, ClinGen CA171654, ClinVar RCV000145546, ClinVar RCV004724924, AlphaMissense 0.99, MetaLR 0.43, Likely pathogenic, CDKL5 disorder; Developmental and epileptic encephalopathy, 2
- E21K (p.Glu21Lys), rs2518776911, ClinGen CA412489611, ClinVar RCV003812299, MetaLR 0.31, MetaSVM -0.36, Pathogenic, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- E21E (p.Glu21Glu), gnomAD X-18507159-A-G, CADD 23.10
- G22A (p.Gly22Ala), rs1602232972, ClinGen CA412489769, ClinVar RCV001089707, ClinVar RCV001593260, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, not provided; Developmental and epileptic encephalopathy, 2
- G22E (p.Gly22Glu), rs1602232972, ClinGen CA412489767, ClinVar RCV000990475, ClinVar RCV001371944, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, CDKL5 disorder
- G22R (p.Gly22Arg), rs1922607139, ClinGen CA412489619, ClinVar RCV001253697, ClinVar RCV005909224, AlphaMissense 1.00, MetaLR 0.97, Likely pathogenic, Developmental and epileptic encephalopathy, 2
- G22G (p.Gly22Gly), gnomAD X-18510821-A-G, CADD 19.10
- A23S (p.Ala23Ser), cosmic curated COSV66112, MetaLR 0.24, MetaSVM -0.61
- A23D (p.Ala23Asp), gnomAD X-18510823-C-A, MetaLR 0.59, MetaSVM 0.41
- A23A (p.Ala23Ala), gnomAD X-18510824-C-A, CADD 12.40
- Y24C (p.Tyr24Cys), rs1922801133, ClinGen CA412489792, ClinVar RCV001253167, ClinVar RCV005225332, MetaLR 0.36, MetaSVM -0.15, Conflicting interpretations, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- Y24H (p.Tyr24His), gnomAD X-18510825-T-C, MetaLR 0.32, MetaSVM -0.35
- Y24Y (p.Tyr24Tyr), gnomAD X-18510827-T-C, CADD 9.25
- G25* (p.Gly25Ter), cosmic curated COSV66112
- G25R (p.Gly25Arg), rs587783130, ClinGen CA294694, ClinVar RCV000144802, Ensembl rs587783130, MetaLR 0.67, MetaSVM 0.70, Pathogenic, not provided
- G25V (p.Gly25Val), rs2518781124, ClinGen CA412489808, ClinVar RCV003807977, Pathogenic, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- G25E (p.Gly25Glu), gnomAD X-18510827-TG-T, CADD 34.00
- G25G (p.Gly25Gly), gnomAD X-18510830-A-G, CADD 18.80
- V26I (p.Val26Ile), gnomAD X-18510831-G-A, MetaLR 0.33, MetaSVM -0.37
- V27A (p.Val27Ala), rs2518781128, ClinGen CA412489831, ClinVar RCV002466381, ClinVar RCV003326633, MetaLR 0.58, MetaSVM 0.32, Pathogenic/Likely pathogenic, CDKL5 disorder; not provided; Developmental and epileptic encephalopathy, 2
- V27E (p.Val27Glu), cosmic curated COSV66110, MetaLR 0.70, MetaSVM 0.71
- V27I (p.Val27Ile), gnomAD X-18510834-G-A, MetaLR 0.58, MetaSVM 0.31
- L28I (p.Leu28Ile), gnomAD X-18510837-C-A, MetaLR 0.25, MetaSVM -0.41
- K29T (p.Lys29Thr), rs2518781132, ClinGen CA412489848, ClinVar RCV002299296, Pathogenic, Angelman syndrome-like; Developmental and epileptic encephalopathy, 2
- C30Y (p.Cys30Tyr), rs1555940536, ClinGen CA412489863, cosmic curated COSV10822, ClinVar RCV000518084, MetaLR 0.22, MetaSVM -0.67, Uncertain significance, CDKL5 disorder
- C30R (p.Cys30Arg), gnomAD X-18510843-T-C, MetaLR 0.21, MetaSVM -0.69
- C30C (p.Cys30Cys), rs891192393, gnomAD X-18510845-C-T, CADD 16.20
- C30* (p.Cys30Ter), gnomAD X-18510845-C-A, CADD 35.00
- R31G (p.Arg31Gly), rs786204991, ClinGen CA199415, ClinVar RCV000170055, ClinVar RCV004725012, MetaLR 0.29, MetaSVM -0.44, Uncertain significance, CDKL5 disorder
- R31R (p.Arg31Arg), rs140332992, gnomAD X-18510848-A-G, CADD 13.30
- H32P (p.His32Pro), cosmic curated COSV66113, MetaLR 0.44, MetaSVM -0.09
- H32Y (p.His32Tyr), gnomAD X-18510849-C-T, MetaLR 0.40, MetaSVM -0.18
- H32N (p.His32Asn), gnomAD X-18510849-C-A, MetaLR 0.23, MetaSVM -0.73
- H32R (p.His32Arg), gnomAD X-18510850-A-G, MetaLR 0.29, MetaSVM -0.44
- H32Q (p.His32Gln), gnomAD X-18510851-C-A, MetaLR 0.28, MetaSVM -0.52
- K33E (p.Lys33Glu), gnomAD X-18510852-A-G, MetaLR 0.20, MetaSVM -0.66
- K33R (p.Lys33Arg), gnomAD X-18510853-A-G, MetaLR 0.14, MetaSVM -0.95
- E34* (p.Glu34Ter), rs2518834440, ClinGen CA412346656, ClinVar RCV003064672, ClinVar RCV005930329, Pathogenic
- E34K (p.Glu34Lys), gnomAD X-18564477-G-A, MetaLR 0.18, MetaSVM -0.76
- E34G (p.Glu34Gly), gnomAD X-18564478-A-G, MetaLR 0.29, MetaSVM -0.49
- E34E (p.Glu34Glu), gnomAD X-18564479-A-G, CADD 15.60
- T35A (p.Thr35Ala), rs1924898828, ClinGen CA412346662, ClinVar RCV003337912, AlphaMissense 0.95, MetaLR 0.28, Uncertain significance, Developmental and epileptic encephalopathy, 2
- T35P (p.Thr35Pro), rs1924898828, ClinGen CA412346664, ClinVar RCV001243962, Ensembl rs1924898828, AlphaMissense 0.95, MetaLR 0.28, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- T35H (p.Thr35His), gnomAD X-18564477-GA-G, CADD 25.20
- T35K (p.Thr35Lys), gnomAD X-18564481-C-A, MetaLR 0.24, MetaSVM -0.62
- T35I (p.Thr35Ile), gnomAD X-18564481-C-T, MetaLR 0.28, MetaSVM -0.49
- T35T (p.Thr35Thr), rs760485617, gnomAD X-18564482-A-G, CADD 6.09
- H36R (p.His36Arg), ExAC rs763985235, TOPMed rs763985235, gnomAD rs763985235, MetaLR 0.04, MetaSVM -1.07, Uncertain significance, not provided
- H36Y (p.His36Tyr), TOPMed rs1170783648, gnomAD rs1170783648, MetaLR 0.12, MetaSVM -0.98
- H36N (p.His36Asn), gnomAD X-18564483-C-A, MetaLR 0.03, MetaSVM -1.03
- H36Q (p.His36Gln), gnomAD X-18564485-T-G, MetaLR 0.05, MetaSVM -1.06
- H36H (p.His36His), gnomAD X-18564485-T-C, CADD 10.60
- E37K (p.Glu37Lys), gnomAD X-18564486-G-A, MetaLR 0.14, MetaSVM -0.86
- E37* (p.Glu37Ter), gnomAD X-18564486-G-T, CADD 37.00
- E37G (p.Glu37Gly), gnomAD X-18564487-A-G, MetaLR 0.34, MetaSVM -0.29
- E37E (p.Glu37Glu), gnomAD X-18564488-A-G, CADD 11.00
- I38S (p.Ile38Ser), rs1555947847, ClinGen CA412346687, ClinVar RCV000497323, Ensembl rs1555947847, AlphaMissense 0.82, MetaLR 0.23, Likely pathogenic, not provided
- I38V (p.Ile38Val), gnomAD X-18564489-A-G, MetaLR 0.12, MetaSVM -0.83
- I38T (p.Ile38Thr), gnomAD X-18564490-T-C, MetaLR 0.20, MetaSVM -0.69
- V39G (p.Val39Gly), rs1924899673, ClinGen CA412346694, ClinVar RCV001063549, Ensembl rs1924899673, MetaLR 0.64, MetaSVM 0.49, Likely pathogenic, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- V39M (p.Val39Met), gnomAD X-18564492-G-A, MetaLR 0.51, MetaSVM 0.17
- V39A (p.Val39Ala), gnomAD X-18564493-T-C, MetaLR 0.46, MetaSVM 0.02
- V39V (p.Val39Val), gnomAD X-18564494-G-T, CADD 10.20
- A40V (p.Ala40Val), rs122460159, ClinGen CA121521, NCI-TCGA Cosmic COSV6611, cosmic curated COSV66113, MetaLR 0.56, MetaSVM 0.36, Pathogenic, CDKL5 disorder
- A40T (p.Ala40Thr), gnomAD X-18564495-G-A, MetaLR 0.73, MetaSVM 0.76
- A40S (p.Ala40Ser), gnomAD X-18564495-G-T, MetaLR 0.67, MetaSVM 0.57
- A40E (p.Ala40Glu), gnomAD X-18564496-C-A, MetaLR 0.70, MetaSVM 0.66
- A40G (p.Ala40Gly), gnomAD X-18564496-C-G, MetaLR 0.70, MetaSVM 0.66
- A40A (p.Ala40Ala), gnomAD X-18564497-G-C, CADD 5.83
- I41F (p.Ile41Phe), rs587783071, ClinGen CA294582, ClinVar RCV000144733, Ensembl rs587783071, AlphaMissense 1.00, MetaLR 0.42, Likely pathogenic, not provided
- I41V (p.Ile41Val), gnomAD X-18564498-A-G, MetaLR 0.17, MetaSVM -0.71
- I41T (p.Ile41Thr), gnomAD X-18564499-T-C, MetaLR 0.46, MetaSVM -0.02
- I41I (p.Ile41Ile), gnomAD X-18564500-C-T, CADD 12.40
- K42R (p.Lys42Arg), rs267608429, ClinGen CA171606, ClinVar RCV000133319, ClinVar RCV000145514, MetaLR 0.79, MetaSVM 0.79, Pathogenic/Likely pathogenic, CDKL5 disorder; Developmental and epileptic encephalopathy, 2
- K42Q (p.Lys42Gln), gnomAD X-18564501-A-C, MetaLR 0.84, MetaSVM 0.89
- K42E (p.Lys42Glu), gnomAD X-18564501-A-G, MetaLR 0.81, MetaSVM 0.83
- K42M (p.Lys42Met), gnomAD X-18564502-A-T, MetaLR 0.84, MetaSVM 0.90
- K42K (p.Lys42Lys), gnomAD X-18564503-G-A, CADD 12.30
- K42N (p.Lys42Asn), gnomAD X-18564503-G-T, MetaLR 0.83, MetaSVM 0.92
- K43E (p.Lys43Glu), gnomAD X-18564504-A-G, MetaLR 0.21, MetaSVM -0.70
- K43* (p.Lys43Ter), gnomAD X-18564504-A-T, CADD 38.00
- K43R (p.Lys43Arg), gnomAD X-18564505-A-G, MetaLR 0.18, MetaSVM -0.74
- K43K (p.Lys43Lys), gnomAD X-18564506-A-G, CADD 9.36
- F44L (p.Phe44Leu), gnomAD X-18564507-T-C, MetaLR 0.11, MetaSVM -0.83
- F44S (p.Phe44Ser), gnomAD X-18564508-T-C, MetaLR 0.30, MetaSVM -0.46
- F44F (p.Phe44Phe), gnomAD X-18564509-C-T, CADD 13.30
- K45E (p.Lys45Glu), rs2147132256, ClinGen CA412346731, ClinVar RCV001786250, Ensembl rs2147132256, MetaLR 0.35, MetaSVM -0.16, Uncertain significance, not provided
- K45N (p.Lys45Asn), rs1602263431, ClinGen CA412346736, ClinVar RCV001296957, Ensembl rs1602263431, MetaLR 0.32, MetaSVM -0.29, Uncertain significance, Angelman syndrome-like; Developmental and epileptic encephalopathy, 2
- K45R (p.Lys45Arg), rs2518834517, ClinGen CA412346734, ClinVar RCV003267949, MetaLR 0.29, MetaSVM -0.44, Uncertain significance, Inborn genetic diseases
- K45* (p.Lys45Ter), gnomAD X-18564510-A-T, CADD 37.00
- K45T (p.Lys45Thr), gnomAD X-18564511-A-C, MetaLR 0.40, MetaSVM -0.06
- K45M (p.Lys45Met), gnomAD X-18564511-A-T, MetaLR 0.47, MetaSVM 0.07
- K45K (p.Lys45Lys), gnomAD X-18564512-G-A, CADD 10.80
- D46G (p.Asp46Gly), Ensembl rs910518253, MetaLR 0.26, MetaSVM -0.54
- D46V (p.Asp46Val), gnomAD X-18564514-A-T, MetaLR 0.27, MetaSVM -0.52
- D46D (p.Asp46Asp), rs2147132270, gnomAD X-18564515-C-T, CADD 10.40
- D46E (p.Asp46Glu), gnomAD X-18564515-C-A, MetaLR 0.20, MetaSVM -0.74
- S47G (p.Ser47Gly), gnomAD X-18564516-A-G, MetaLR 0.14, MetaSVM -0.91
- S47N (p.Ser47Asn), gnomAD X-18564517-G-A, MetaLR 0.29, MetaSVM -0.38
- S47S (p.Ser47Ser), gnomAD X-18564518-T-C, CADD 9.46
- S47R (p.Ser47Arg), gnomAD X-18564518-T-A, MetaLR 0.23, MetaSVM -0.74
- E48D (p.Glu48Asp), cosmic curated COSV10118, MetaLR 0.21, MetaSVM -0.81
- E48K (p.Glu48Lys), gnomAD X-18564519-G-A, MetaLR 0.16, MetaSVM -0.76
- E48* (p.Glu48Ter), gnomAD X-18564519-G-T, CADD 37.00
- E48G (p.Glu48Gly), gnomAD X-18564520-A-G, MetaLR 0.23, MetaSVM -0.60
- E48E (p.Glu48Glu), gnomAD X-18564521-A-G, CADD 23.20
- E49K (p.Glu49Lys), gnomAD X-18564519-GA-G, CADD 31.00
- E49* (p.Glu49Ter), gnomAD X-18564522-G-T, CADD 57.00
- E52* (p.Glu52Ter), rs1925261282, ClinGen CA412348490, cosmic curated COSV10971, ClinVar RCV001067845, Pathogenic
- E52Q (p.Glu52Gln), cosmic curated COSV66110, MetaLR 0.25, MetaSVM -0.57
- V53D (p.Val53Asp), gnomAD X-18575366-T-A, MetaLR 0.27, MetaSVM -0.44
- V53V (p.Val53Val), gnomAD X-18575367-C-A, CADD 10.80
- E55* (p.Glu55Ter), rs2518844542, ClinGen CA412348533, ClinVar RCV003808679, Pathogenic
- E55D (p.Glu55Asp), gnomAD X-18575373-A-C, MetaLR 0.23, MetaSVM -0.65
- E55E (p.Glu55Glu), gnomAD X-18575373-A-G, CADD 9.88, SIFT 0.05
- T56M (p.Thr56Met), rs774865696, NCI-TCGA Cosmic COSV6611, cosmic curated COSV66110, ExAC rs774865696, MetaLR 0.47, MetaSVM -0.04, Variant assessed as somatic; moderate impact.
- T56T (p.Thr56Thr), rs759058148, gnomAD X-18575376-G-A, CADD 12.40, SIFT 0.06
- T57S (p.Thr57Ser), 1000Genomes rs2147139542, MetaLR 0.15, MetaSVM -0.76
- L58* (p.Leu58Ter), rs875989950, ClinGen CA10576343, ClinVar RCV000211584, Ensembl rs875989950, Pathogenic
- R59* (p.Arg59Ter), rs62653623, ClinGen CA171618, NCI-TCGA Cosmic COSV6611, cosmic curated COSV66112, Pathogenic
- R59L (p.Arg59Leu), cosmic curated COSV10118
- R59P (p.Arg59Pro), rs1555949009, ClinGen CA412348582, ClinVar RCV000585862, ClinVar RCV005053950, AlphaMissense 1.00, MetaLR 0.33, Likely pathogenic, CDKL5 disorder; Developmental and epileptic encephalopathy, 2
- R59Q (p.Arg59Gln), rs1555949009, ClinGen CA412348584, NCI-TCGA Cosmic COSV1011, NCI-TCGA Cosmic COSV6611, AlphaMissense 1.00, MetaLR 0.33, Uncertain significance, CDKL5 disorder
- E60G (p.Glu60Gly), rs2518844580, ClinGen CA412348596, ClinVar RCV003806293, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- E60K (p.Glu60Lys), rs1925262394, ClinGen CA412348586, ClinVar RCV001752799, Ensembl rs1925262394, AlphaMissense 1.00, MetaLR 0.85, Uncertain significance, not provided
- E60Q (p.Glu60Gln), rs1925262394, ClinGen CA412348590, ClinVar RCV001089713, Ensembl rs1925262394, AlphaMissense 1.00, MetaLR 0.85, Uncertain significance, Developmental and epileptic encephalopathy, 2
- E60E (p.Glu60Glu), rs148697943, gnomAD X-18575388-G-A, CADD 10.40, SIFT 0.00
- K62T (p.Lys62Thr), cosmic curated COSV10532, MetaLR 0.36, MetaSVM -0.27
- M63I (p.Met63Ile), NCI-TCGA Cosmic COSV1011, cosmic curated COSV10118, MetaLR 0.08, MetaSVM -0.50, Uncertain significance, Angelman syndrome-like; Developmental and epileptic encephalopathy, 2
- M63V (p.Met63Val), gnomAD X-18575395-A-G, MetaLR 0.08, MetaSVM -0.98
- L64P (p.Leu64Pro), rs267608435, ClinGen CA170460, ClinVar RCV000133335, ClinVar RCV004724851, AlphaMissense 1.00, MetaLR 0.53, Uncertain significance, CDKL5 disorder
- L64L (p.Leu64Leu), rs145496868, gnomAD X-18575400-T-G, CADD 9.89
- R65P (p.Arg65Pro), rs267608436, ClinGen CA412348630, ClinVar RCV001385375, ExAC rs267608436, AlphaMissense 1.00, MetaLR 0.54, Pathogenic, Angelman syndrome-like; Developmental and epileptic encephalopathy, 2
- R65Q (p.Arg65Gln), rs267608436, ClinGen CA170462, cosmic curated COSV66111, ClinVar RCV000133336, AlphaMissense 1.00, MetaLR 0.54, Likely benign, CDKL5 disorder
- T66T (p.Thr66Thr), gnomAD X-18575406-T-C, CADD 9.69
- L67F (p.Leu67Phe), rs267608437, ClinGen CA170464, ClinVar RCV000133338, ClinVar RCV000145527, AlphaMissense 0.99, MetaLR 0.50, Uncertain significance, CDKL5 disorder
- K68Q (p.Lys68Gln), gnomAD X-18575410-A-C, MetaLR 0.15, MetaSVM -0.92
- Q69* (p.Gln69Ter), rs2518844612, ClinGen CA412348653, ClinVar RCV002421943, ClinVar RCV005869828, Pathogenic
- Q69P (p.Gln69Pro), rs2518844618, ClinGen CA412348654, ClinVar RCV003022046, Uncertain significance, Developmental and epileptic encephalopathy, 2; Angelman syndrome-like
- E70D (p.Glu70Asp), TOPMed rs1925264018, gnomAD rs1925264018, MetaLR 0.06, MetaSVM -1.04
- E70K (p.Glu70Lys), cosmic curated COSV66113, MetaLR 0.13, MetaSVM -0.84
- N71D (p.Asn71Asp), rs587783072, ClinGen CA199365, ClinVar RCV000144734, ClinVar RCV000169981, AlphaMissense 0.97, MetaLR 0.45, Conflicting interpretations, CDKL5 disorder; not provided
- N71K (p.Asn71Lys), rs1602269367, ClinGen CA412348673, ClinVar RCV000990476, Ensembl rs1602269367, AlphaMissense 1.00, MetaLR 0.44, Likely pathogenic, Developmental and epileptic encephalopathy, 2
Public CDKL5 analysis runs
- CDKL5 analysis run — CDKL5 (1,181 variants) — completed 2026-08-18