SCN2A (Q99250) variants and mutations
SCN2A (also known as Q99250) is a human protein-coding gene encoding a sodium channel protein type 2 subunit alpha protein. The protein forms Nav1.2, a voltage-gated sodium channel that carries sodium current during neuronal action potentials. By shaping neuronal excitability and signal propagation, it supports brain circuits involved in development, learning, and seizure susceptibility. This analysis covers 3,433 SCN2A variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes developmental and epileptic encephalopathy, 11, seizures, benign familial infantile, 3, and Seizure. Example SCN2A variants include M1?, M1L, and A2?.
Variant analysis overview
- Gene: SCN2A
- Protein: Q99250
- UniProt accession: Q99250
- Organism: Homo sapiens
- Variants analyzed: 3433
- Variant scope: all variants
- Completed: 2026-06-04
Variant and mutation evidence
- Variant composition: 3,224 unspecified-consequence records; 94 synonymous variants; 94 missense variants; 1 in-frame insertions; 7 frameshift variants; 6 splice-region variants; 1 stop-gained variants; 6 substitution
- Prediction scores: 2,964 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental and epileptic encephalopathy, 11, seizures, benign familial infantile, 3, Seizure, episodic ataxia, type 9, bipolar disorder, epilepsy, complex neurodevelopmental disorder, partial epilepsy, infantile spasms, Benign familial neonatal-infantile seizures, Pain, benign familial infantile epilepsy.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 34 post-translational modification sites.
- Structural context: 780 variants have structural context.
- PTM context: 49 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, PharmGKB, MaveDB, LitVar.
Notable SCN2A variants
Examples include M1?, M1L, A2?, A2T, Q3*, Q3H, Q3R, Q3Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10804
- M1L (p.Met1Leu), rs1553564139, ClinGen CA349009610, ClinVar RCV000677679, ESM-1b 0.34, AlphaMissense 0.31, Likely pathogenic, Developmental and epileptic encephalopathy, 11
- A2?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A2T (p.Ala2Thr), gnomAD rs1274697462, REVEL 0.65, ESM-1b 0.00
- Q3* (p.Gln3Ter), rs1553564141, ClinGen CA349009632, ClinVar RCV001236295, Ensembl rs1553564141, Pathogenic
- Q3H (p.Gln3His), rs1435672829, ClinGen CA349009640, ClinVar RCV002884267, ESM-1b 0.00, AlphaMissense 0.26, Uncertain significance, Inborn genetic diseases
- Q3R (p.Gln3Arg), rs1181276453, ClinGen CA349009637, ClinVar RCV003785703, TOPMed rs1181276453, REVEL 0.50, ESM-1b 0.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- Q3Q (p.Gln3Gln), rs1435672829, gnomAD 2-165295832-G-A, CADD 6.69
- S4* (p.Ser4Ter), rs1553564144, cosmic curated COSV51832, ClinGen CA349009650, ClinVar RCV000504449, CADD 36.00, Pathogenic
- V5M (p.Val5Met), rs2467837698, ClinGen CA349009653, ClinVar RCV003802822, REVEL 0.43, ESM-1b 0.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- V5A (p.Val5Ala), gnomAD 2-165295837-T-C, REVEL 0.52, ESM-1b 0.00
- L6M (p.Leu6Met), rs2467837709, ClinGen CA349009662, ClinVar RCV002290312, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance, Developmental and epileptic encephalopathy, 11
- L6L (p.Leu6Leu), gnomAD 2-165295841-G-A, CADD 11.30
- V7I (p.Val7Ile), gnomAD 2-165295842-G-A, REVEL 0.46, ESM-1b 0.00
- V7L (p.Val7Leu), gnomAD 2-165295842-G-C, REVEL 0.35, ESM-1b 0.00
- P8L (p.Pro8Leu), rs747139785, ClinGen CA318054, ClinVar RCV000189184, ClinVar RCV001062691, REVEL 0.75, ESM-1b 1.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- P8Q (p.Pro8Gln), rs747139785, ClinGen CA349009684, NCI-TCGA Cosmic COSV9932, cosmic curated COSV99329, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- P8P (p.Pro8Pro), rs149534277, gnomAD 2-165295847-G-T, CADD 1.76
- P9S (p.Pro9Ser), TOPMed rs1469809588, gnomAD rs1469809588, REVEL 0.80, ESM-1b 0.25
- P9Q (p.Pro9Gln), gnomAD 2-165295849-C-A, REVEL 0.77, ESM-1b 0.16
- P9P (p.Pro9Pro), rs1191664110, gnomAD 2-165295850-A-T, CADD 12.40
- G10* (p.Gly10Ter), Ensembl rs1553564147
- G10E (p.Gly10Glu), cosmic curated COSV51843, ESM-1b 1.00, AlphaMissense 0.95
- G10K (p.Gly10Lys), cosmic curated COSV10510, ESM-1b 1.00, AlphaMissense 0.98
- G10R (p.Gly10Arg), cosmic curated COSV10462, ESM-1b 1.00, AlphaMissense 0.96
- G10V (p.Gly10Val), NCI-TCGA Cosmic COSV5184, NCI-TCGA Cosmic COSV9933, cosmic curated COSV99330, ESM-1b 1.00, AlphaMissense 0.87, Variant assessed as somatic; moderate impact.
- P11A (p.Pro11Ala), rs2106148959, ClinGen CA349009710, ClinVar RCV001776391, Ensembl rs2106148959, ESM-1b 0.33, AlphaMissense 0.22, Uncertain significance, not provided
- P11H (p.Pro11His), gnomAD 2-165295855-C-A, REVEL 0.76, ESM-1b 1.00
- P11R (p.Pro11Arg), gnomAD 2-165295855-C-G, REVEL 0.77, ESM-1b 1.00
- P11P (p.Pro11Pro), gnomAD 2-165295856-T-C, CADD 14.90
- D12E (p.Asp12Glu), rs1334730213, ClinGen CA349009727, ClinVar RCV001034090, TOPMed rs1334730213, REVEL 0.34, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases
- D12N (p.Asp12Asn), rs1696475965, ClinGen CA349009717, ClinVar RCV002319766, Ensembl rs1696475965, ESM-1b 0.04, AlphaMissense 0.15, Pathogenic
- D12V (p.Asp12Val), gnomAD 2-165295858-A-T, REVEL 0.86, ESM-1b 1.00
- D12G (p.Asp12Gly), gnomAD 2-165295858-A-G, REVEL 0.73, ESM-1b 1.00
- D12D (p.Asp12Asp), rs1334730213, gnomAD 2-165295859-C-T, CADD 12.40
- S13G (p.Ser13Gly), rs2106148981, ClinGen CA349009731, ClinVar RCV001759084, Ensembl rs2106148981, ESM-1b 0.36, AlphaMissense 0.25, Uncertain significance, not provided
- F14L (p.Phe14Leu), cosmic curated COSV10730, ESM-1b 1.00, AlphaMissense 0.79
- R15C (p.Arg15Cys), rs551347418, ClinGen CA1939539, NCI-TCGA Cosmic COSV5185, cosmic curated COSV51853, REVEL 0.69, ESM-1b 1.00, Conflicting interpretations, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- R15H (p.Arg15His), rs773482307, ClinGen CA1939541, cosmic curated COSV51833, ClinVar RCV003077224, REVEL 0.48, ESM-1b 1.00, Likely benign, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- R15L (p.Arg15Leu), ExAC rs773482307, TOPMed rs773482307, gnomAD rs773482307, ESM-1b 1.00, AlphaMissense 0.16, Likely benign
- R15S (p.Arg15Ser), 1000Genomes rs551347418, ExAC rs551347418, gnomAD rs551347418, REVEL 0.72, ESM-1b 1.00, Likely benign
- F16C (p.Phe16Cys), ExAC rs763488120, gnomAD rs763488120, REVEL 0.50, ESM-1b 0.00
- F16L (p.Phe16Leu), Ensembl rs1696476663, REVEL 0.23, ESM-1b 0.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- F17I (p.Phe17Ile), NCI-TCGA Cosmic COSV5185, cosmic curated COSV51850, ESM-1b 1.00, AlphaMissense 0.84, Variant assessed as somatic; moderate impact.
- F17L (p.Phe17Leu), gnomAD 2-165295874-T-A, REVEL 0.67, ESM-1b 0.90
- T18N (p.Thr18Asn), cosmic curated COSV51839, ESM-1b 1.00, AlphaMissense 0.17
- T18A (p.Thr18Ala), gnomAD 2-165295875-A-G, REVEL 0.60, ESM-1b 1.00
- R19K (p.Arg19Lys), rs17183814, ClinGen CA155062, cosmic curated COSV51834, ClinVar RCV000118260, ESM-1b 0.00, AlphaMissense 0.08, Benign, Complex neurodevelopmental disorder
- R19M (p.Arg19Met), cosmic curated COSV10587, ESM-1b 1.00, AlphaMissense 0.24
- R19S (p.Arg19Ser), rs1409575197, gnomAD rs1409575197, REVEL 0.60, ESM-1b 0.70, Variant assessed as somatic; moderate impact.
- E20* (p.Glu20Ter), gnomAD rs1165991893
- E20D (p.Glu20Asp), TOPMed rs1696477720, ESM-1b 0.00, AlphaMissense 0.13
- E20K (p.Glu20Lys), gnomAD rs1165991893, REVEL 0.78, ESM-1b 1.00
- S21Y (p.Ser21Tyr), gnomAD 2-165295885-C-A, REVEL 0.92, ESM-1b 1.00
- S21S (p.Ser21Ser), gnomAD 2-165295886-C-T, CADD 9.72
- L22F (p.Leu22Phe), TOPMed rs1449575863, gnomAD rs1449575863, REVEL 0.77, ESM-1b 1.00
- L22I (p.Leu22Ile), cosmic curated COSV51845, ESM-1b 1.00, AlphaMissense 0.25
- L22V (p.Leu22Val), TOPMed rs1449575863, gnomAD rs1449575863, ESM-1b 1.00, AlphaMissense 0.26
- A23S (p.Ala23Ser), Ensembl rs1574524925, ESM-1b 0.00, AlphaMissense 0.12
- A23A (p.Ala23Ala), rs773988733, gnomAD 2-165295892-T-G, CADD 13.30
- A24T (p.Ala24Thr), rs527452801, ClinGen CA318057, cosmic curated COSV10730, ClinVar RCV000713078, REVEL 0.49, ESM-1b 0.36, Benign/Likely benign, Inborn genetic diseases; Developmental and epileptic encephalopathy, 11; Seizure
- A24V (p.Ala24Val), NCI-TCGA TCGA novel, ESM-1b 0.00, AlphaMissense 0.14, Variant assessed as somatic; moderate impact.
- p.Ala24dup, gnomAD 2-165295888-T-TTG, CADD 19.30
- I25M (p.Ile25Met), Ensembl rs1029316443, ESM-1b 1.00, AlphaMissense 0.15
- I25S (p.Ile25Ser), rs1366486532, ClinGen CA349009866, ClinVar RCV001753391, TOPMed rs1366486532, ESM-1b 1.00, AlphaMissense 0.78, Uncertain significance, not provided
- I25T (p.Ile25Thr), rs1366486532, ClinGen CA349009864, ClinVar RCV001961336, TOPMed rs1366486532, REVEL 0.92, ESM-1b 1.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- I25V (p.Ile25Val), rs767145207, ClinGen CA1939544, NCI-TCGA Cosmic COSV9933, cosmic curated COSV99333, REVEL 0.73, ESM-1b 1.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- E26K (p.Glu26Lys), cosmic curated COSV10510, ESM-1b 1.00, AlphaMissense 0.41
- E26Q (p.Glu26Gln), rs1439524882, ClinGen CA349009870, ClinVar RCV001786713, ClinVar RCV005732477, REVEL 0.74, ESM-1b 1.00, Uncertain significance, not provided; Inborn genetic diseases
- Q27* (p.Gln27Ter), Ensembl rs1553564165
- Q27H (p.Gln27His), rs1162322343, ClinGen CA349009893, ClinVar RCV001768319, TOPMed rs1162322343, REVEL 0.55, ESM-1b 0.73, Uncertain significance, not provided
- R28C (p.Arg28Cys), rs200884216, ClinGen CA318060, cosmic curated COSV51834, ClinVar RCV000335873, REVEL 0.70, ESM-1b 1.00, Benign/Likely benign, Inborn genetic diseases; Developmental and epileptic encephalopathy, 11; Seizure
- R28H (p.Arg28His), rs1007052146, ClinGen CA59719605, NCI-TCGA Cosmic COSV5183, cosmic curated COSV51833, REVEL 0.67, ESM-1b 1.00, Conflicting interpretations, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- R28L (p.Arg28Leu), gnomAD 2-165295906-G-T, REVEL 0.71, ESM-1b 1.00
- I29T (p.Ile29Thr), ESP rs370552463, REVEL 0.75, ESM-1b 1.00
- I29F (p.Ile29Phe), gnomAD 2-165295908-A-T, REVEL 0.62, ESM-1b 1.00
- I29I (p.Ile29Ile), gnomAD 2-165295910-T-C, CADD 12.30
- A30T (p.Ala30Thr), rs1337092354, ClinGen CA349009913, ClinVar RCV000696489, gnomAD rs1337092354, REVEL 0.50, ESM-1b 0.86, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- E31D (p.Glu31Asp), gnomAD rs1696479768, REVEL 0.57, ESM-1b 0.27
- E31K (p.Glu31Lys), rs2467838141, ClinGen CA349009927, ClinVar RCV003329066, ESM-1b 1.00, AlphaMissense 0.14, Uncertain significance, not provided
- E32* (p.Glu32Ter), Ensembl rs1553564169
- E32Q (p.Glu32Gln), gnomAD 2-165295917-G-C, REVEL 0.61, ESM-1b 1.00
- K33* (p.Lys33Ter), Ensembl rs1553564172
- A34T (p.Ala34Thr), rs144814658, ClinGen CA318063, ClinVar RCV000189187, ClinVar RCV000282210, REVEL 0.73, ESM-1b 0.57, Conflicting interpretations, Inborn genetic diseases; Developmental and epileptic encephalopathy, 11; Seizure
- A34V (p.Ala34Val), rs1553564177, ClinGen CA349009970, ClinVar RCV000622964, Ensembl rs1553564177, REVEL 0.73, ESM-1b 0.96, Uncertain significance, Inborn genetic diseases
- K35* (p.Lys35Ter), Ensembl rs1553564178
- K35N (p.Lys35Asn), NCI-TCGA Cosmic COSV5183, cosmic curated COSV51833, ESM-1b 0.00, AlphaMissense 0.23, Variant assessed as somatic; moderate impact.
- R36* (p.Arg36Ter), TOPMed rs796053167, gnomAD rs796053167, Uncertain significance
- R36G (p.Arg36Gly), rs796053167, ClinGen CA318066, ClinVar RCV000189188, ClinVar RCV000764276, REVEL 0.26, ESM-1b 0.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- R36K (p.Arg36Lys), NCI-TCGA Cosmic COSV5183, cosmic curated COSV51831, REVEL 0.28, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- R36R (p.Arg36Arg), rs796053167, gnomAD 2-165295929-A-C, CADD 12.50
- P37R (p.Pro37Arg), rs2467838210, ClinGen CA349010002, ClinVar RCV003809815, ESM-1b 0.27, AlphaMissense 0.13, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- P37S (p.Pro37Ser), ExAC rs763906285, gnomAD rs763906285, REVEL 0.31, ESM-1b 0.57, Uncertain significance
- P37T (p.Pro37Thr), rs763906285, ClinGen CA349009995, ClinVar RCV001231764, ExAC rs763906285, ESM-1b 0.88, AlphaMissense 0.09, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- K38* (p.Lys38Ter), cosmic curated COSV51840, Ensembl rs1553564186
- K38T (p.Lys38Thr), rs2467838227, ClinGen CA349010017, ClinVar RCV003321282, REVEL 0.65, ESM-1b 0.00, Uncertain significance, not provided
- K38R (p.Lys38Arg), gnomAD 2-165295936-A-G, REVEL 0.53, ESM-1b 0.00
- K38K (p.Lys38Lys), rs753614123, gnomAD 2-165295937-A-G, CADD 8.52
- Q39* (p.Gln39Ter), ExAC rs757194863, TOPMed rs757194863, gnomAD rs757194863, Uncertain significance
- Q39K (p.Gln39Lys), rs757194863, ClinGen CA1939548, ClinVar RCV002033493, ExAC rs757194863, REVEL 0.32, ESM-1b 0.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- Q39R (p.Gln39Arg), ExAC rs778773546, REVEL 0.22, ESM-1b 0.00
- Q39Q (p.Gln39Gln), gnomAD 2-165295940-G-A, CADD 7.02
- E40* (p.Glu40Ter), Ensembl rs1553564192, Uncertain significance
- E40K (p.Glu40Lys), rs1553564192, ClinGen CA349010031, ClinVar RCV001304707, Ensembl rs1553564192, REVEL 0.31, ESM-1b 0.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- E40E (p.Glu40Glu), gnomAD 2-165295943-A-G, CADD 8.68
- R41C (p.Arg41Cys), rs747086776, ClinGen CA1939550, NCI-TCGA Cosmic COSV5183, cosmic curated COSV51837, REVEL 0.50, ESM-1b 0.00, Conflicting interpretations, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- R41G (p.Arg41Gly), cosmic curated COSV51854, ESM-1b 0.00, AlphaMissense 0.12
- R41H (p.Arg41His), rs754993031, ClinGen CA1939551, NCI-TCGA Cosmic COSV5184, cosmic curated COSV51849, REVEL 0.27, ESM-1b 0.00, Conflicting interpretations, Seizures, benign familial infantile, 3; SCN2A-related disorder; Developmental an
- R41L (p.Arg41Leu), rs754993031, ClinGen CA349010054, ClinVar RCV001920987, ClinVar RCV003318703, REVEL 0.36, ESM-1b 0.00, Uncertain significance, not provided; Seizures, benign familial infantile, 3; Developmental and epilepti
- R41R (p.Arg41Arg), gnomAD 2-165295946-C-T, CADD 11.60
- K42* (p.Lys42Ter), Ensembl rs1553564197
- K42N (p.Lys42Asn), cosmic curated COSV51836, NCI-TCGA Cosmic COSV5183, NCI-TCGA Cosmic COSV5184, ESM-1b 0.00, AlphaMissense 0.19, Variant assessed as somatic; moderate impact.
- D43N (p.Asp43Asn), cosmic curated COSV51840, gnomAD rs1696482581, REVEL 0.38, ESM-1b 0.00
- D43E (p.Asp43Glu), gnomAD 2-165295952-T-G, REVEL 0.28, ESM-1b 0.00
- E44* (p.Glu44Ter), Ensembl rs1553564200
- E44G (p.Glu44Gly), cosmic curated COSV51854, ESM-1b 0.00, AlphaMissense 0.08
- E44K (p.Glu44Lys), NCI-TCGA Cosmic COSV5184, cosmic curated COSV51842, Ensembl rs1553564200, REVEL 0.34, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- E44E (p.Glu44Glu), rs781272663, gnomAD 2-165295955-G-A, CADD 6.69
- D45G (p.Asp45Gly), ExAC rs748331725, TOPMed rs748331725, gnomAD rs748331725, REVEL 0.61, ESM-1b 0.00, Uncertain significance
- D45V (p.Asp45Val), rs748331725, ClinGen CA349010106, ClinVar RCV000688115, ClinVar RCV001592870, ESM-1b 0.22, AlphaMissense 0.13, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- D45E (p.Asp45Glu), gnomAD 2-165295958-T-A, REVEL 0.47, ESM-1b 0.00
- D46N (p.Asp46Asn), Ensembl rs962766268, REVEL 0.47, ESM-1b 0.00
- D46D (p.Asp46Asp), rs145233994, gnomAD 2-165295961-T-C, CADD 8.54
- D46E (p.Asp46Glu), gnomAD 2-165295961-T-A, REVEL 0.26, ESM-1b 0.00
- E47* (p.Glu47Ter), Ensembl rs1553564206
- E47D (p.Glu47Asp), TOPMed rs1384766755, gnomAD rs1384766755, REVEL 0.32, ESM-1b 0.00
- E47G (p.Glu47Gly), gnomAD 2-165295963-A-G, REVEL 0.65, ESM-1b 0.00
- N48H (p.Asn48His), TOPMed rs1380861945, gnomAD rs1380861945, REVEL 0.46, ESM-1b 0.45
- N48K (p.Asn48Lys), gnomAD 2-165295967-T-G, REVEL 0.40, ESM-1b 0.00
- G49C (p.Gly49Cys), NCI-TCGA Cosmic COSV9933, cosmic curated COSV99333, ESM-1b 0.27, AlphaMissense 0.18, Variant assessed as somatic; moderate impact.
- G49S (p.Gly49Ser), rs773605666, ClinGen CA1939555, ClinVar RCV001943285, ClinVar RCV002388826, REVEL 0.41, ESM-1b 0.00, Uncertain significance, not provided; Inborn genetic diseases; Seizures, benign familial infantile, 3
- G49G (p.Gly49Gly), rs1182973696, gnomAD 2-165295970-C-T, CADD 9.75
- P50Q (p.Pro50Gln), rs2106149256, ClinGen CA349010186, cosmic curated COSV99332, ClinVar RCV002274562, ESM-1b 0.72, AlphaMissense 0.29, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- P50S (p.Pro50Ser), rs2467838602, ClinGen CA349010181, ClinVar RCV003782156, ESM-1b 0.51, AlphaMissense 0.32, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- P50A (p.Pro50Ala), gnomAD 2-165295971-C-G, REVEL 0.71, ESM-1b 0.26
- K51* (p.Lys51Ter), Ensembl rs1553564210
- P52Q (p.Pro52Gln), cosmic curated COSV99331, ESM-1b 1.00, AlphaMissense 0.84
- P52S (p.Pro52Ser), cosmic curated COSV51847, ExAC rs749676317, ESM-1b 1.00, AlphaMissense 0.82, Uncertain significance, not provided
- P52T (p.Pro52Thr), cosmic curated COSV99032, ESM-1b 1.00, AlphaMissense 0.81
- P52L (p.Pro52Leu), gnomAD 2-165295978-C-T, REVEL 0.73, ESM-1b 1.00
- N53D (p.Asn53Asp), cosmic curated COSV99334, ESM-1b 1.00, AlphaMissense 0.30
- N53K (p.Asn53Lys), NCI-TCGA Cosmic COSV5185, cosmic curated COSV51858, ESM-1b 1.00, AlphaMissense 0.69, Variant assessed as somatic; moderate impact.
- N53S (p.Asn53Ser), rs2467838632, ClinGen CA349010236, ClinVar RCV003060436, REVEL 0.39, ESM-1b 0.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- N53I (p.Asn53Ile), gnomAD 2-165295981-A-T, REVEL 0.72, ESM-1b 1.00
- N53N (p.Asn53Asn), gnomAD 2-165295982-C-T, CADD 5.73
- S54C (p.Ser54Cys), rs557687080, ClinGen CA349010249, ClinVar RCV001326364, gnomAD rs557687080, REVEL 0.68, ESM-1b 0.00, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- S54G (p.Ser54Gly), rs557687080, ClinGen CA59719633, ClinVar RCV002274735, gnomAD rs557687080, REVEL 0.53, ESM-1b 0.00, Uncertain significance, not provided
- S54N (p.Ser54Asn), rs1475242235, ClinGen CA349010252, ClinVar RCV003884180, gnomAD rs1475242235, REVEL 0.52, ESM-1b 0.00, Likely benign, not provided
- S54R (p.Ser54Arg), gnomAD 2-165295985-T-A, REVEL 0.70, ESM-1b 1.00
- D55A (p.Asp55Ala), rs1574525321, ClinGen CA349010265, ClinVar RCV001027536, Ensembl rs1574525321, ESM-1b 1.00, AlphaMissense 0.89, Likely pathogenic, Epileptic encephalopathy
- D55H (p.Asp55His), rs2467838667, ClinGen CA349010261, ClinVar RCV003801117, ESM-1b 1.00, AlphaMissense 0.92, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- D55N (p.Asp55Asn), rs2467838667, ClinGen CA349010260, ClinVar RCV003801129, ClinVar RCV004801404, REVEL 0.74, ESM-1b 1.00, Uncertain significance, not provided; Seizures, benign familial infantile, 3; Developmental and epilepti
- D55V (p.Asp55Val), cosmic curated COSV99334, ESM-1b 1.00, AlphaMissense 0.89, Uncertain significance, Developmental and epileptic encephalopathy, 11; Seizures, benign familial infant
- L56* (p.Leu56Ter), rs1553564213, ClinGen CA349010286, ClinVar RCV001265264, Ensembl rs1553564213, Pathogenic
- L56F (p.Leu56Phe), cosmic curated COSV99330, ESM-1b 1.00, AlphaMissense 0.80
- L56M (p.Leu56Met), NCI-TCGA Cosmic COSV5183, cosmic curated COSV51832, NCI-TCGA Cosmic COSV9933, ESM-1b 0.00, AlphaMissense 0.39, Variant assessed as somatic; moderate impact.
- L56S (p.Leu56Ser), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.98, Variant assessed as somatic; moderate impact.
- L56V (p.Leu56Val), cosmic curated COSV99333, ESM-1b 1.00, AlphaMissense 0.34
- L56L (p.Leu56Leu), gnomAD 2-165295991-G-A, CADD 9.31
- E57* (p.Glu57Ter), Ensembl rs1553564214
- E57K (p.Glu57Lys), gnomAD 2-165295992-G-A, REVEL 0.75, ESM-1b 1.00
- A58T (p.Ala58Thr), TOPMed rs1468468653, ESM-1b 1.00, AlphaMissense 0.41
- G59G (p.Gly59Gly), rs796053110, gnomAD 2-165296000-A-C, CADD 10.30
- K60* (p.Lys60Ter), Ensembl rs1553564219
- K60R (p.Lys60Arg), rs1696487020, ClinGen CA349010363, ClinVar RCV001301912, Ensembl rs1696487020, REVEL 0.71, ESM-1b 0.00, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- S61C (p.Ser61Cys), TOPMed rs1696487215, gnomAD rs1696487215, REVEL 0.66, ESM-1b 1.00
- S61F (p.Ser61Phe), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.27, Variant assessed as somatic; moderate impact.
- S61Y (p.Ser61Tyr), NCI-TCGA TCGA novel, TOPMed rs1696487215, gnomAD rs1696487215, ESM-1b 1.00, AlphaMissense 0.21, Variant assessed as somatic; moderate impact.
- S61S (p.Ser61Ser), gnomAD 2-165296006-T-C, CADD 9.21
- L62R (p.Leu62Arg), NCI-TCGA TCGA novel, REVEL 0.86, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- L62V (p.Leu62Val), NCI-TCGA Cosmic COSV5183, cosmic curated COSV51837, ESM-1b 0.25, AlphaMissense 0.22, Variant assessed as somatic; moderate impact.
- P63L (p.Pro63Leu), cosmic curated COSV10730, ESM-1b 1.00, AlphaMissense 0.88, Uncertain significance, Seizures, benign familial infantile, 3; Developmental and epileptic encephalopat
- P63S (p.Pro63Ser), rs1064797259, ClinGen CA16621759, cosmic curated COSV51845, ClinVar RCV000487613, REVEL 0.88, ESM-1b 1.00, Uncertain significance, not provided; Seizures, benign familial infantile, 3; Developmental and epilepti
- F64C (p.Phe64Cys), cosmic curated COSV51837, ESM-1b 1.00, AlphaMissense 0.71
- F64L (p.Phe64Leu), gnomAD 2-165296013-T-C, REVEL 0.73, ESM-1b 0.00
- I65F (p.Ile65Phe), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.67, Variant assessed as somatic; moderate impact.
- I65T (p.Ile65Thr), gnomAD rs1188923931, REVEL 0.92, ESM-1b 1.00
- I65V (p.Ile65Val), gnomAD 2-165296016-A-G, REVEL 0.67, ESM-1b 0.48
- Y66F (p.Tyr66Phe), cosmic curated COSV10959, ESM-1b 1.00, AlphaMissense 0.33
- G67* (p.Gly67Ter), cosmic curated COSV99332, gnomAD rs1420211398
Public SCN2A analysis runs
- SCN2A analysis run — SCN2A (3,433 variants) — completed 2026-06-04