Seizures, benign familial infantile, 3: genes and variants
Explore variant evidence for Seizures, benign familial infantile, 3 across 5 analyzed proteins (SCN2A, KCNQ2, SCN8A, KCNQ3, PRRT2). Linked ClinVar records include 247 pathogenic or likely pathogenic variants, 675 variants of uncertain significance and 119 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
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Genes linked to Seizures, benign familial infantile, 3
SCN2A: Sodium channel protein type 2 subunit alpha
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.
167 ClinVar pathogenic / likely pathogenic and 688 uncertain variants in SCN2A have source records linked to Seizures, benign familial infantile, 3. Association strength is not clinical gene validity.
KCNQ2: Potassium voltage-gated channel subfamily KQT member 2
Together with KCNQ3, its slowly activating potassium current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants cause a spectrum from self-limited familial neonatal epilepsy to severe developmental and epileptic encephalopathy.
57 ClinVar pathogenic / likely pathogenic and 28 uncertain variants in KCNQ2 have source records linked to Seizures, benign familial infantile, 3. Association strength is not clinical gene validity.
SCN8A: Sodium channel protein type 8 subunit alpha
The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.
12 ClinVar pathogenic / likely pathogenic and 25 uncertain variants in SCN8A have source records linked to Seizures, benign familial infantile, 3. Association strength is not clinical gene validity.
KCNQ3: Potassium voltage-gated channel subfamily KQT member 3
Together with KCNQ2, its slowly activating current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants can cause self-limited neonatal epilepsy or more severe developmental and epileptic encephalopathy.
8 ClinVar pathogenic / likely pathogenic and 43 uncertain variants in KCNQ3 have source records linked to Seizures, benign familial infantile, 3. Association strength is not clinical gene validity.
PRRT2: Proline-rich transmembrane protein 2
It modulates presynaptic neurotransmitter release and neuronal excitability through interactions with SNARE machinery and ion channels. Haploinsufficiency commonly causes paroxysmal kinesigenic dyskinesia, self-limited infantile seizures, or the combined infantile-convulsions-and-choreoathetosis phenotype.
3 ClinVar pathogenic / likely pathogenic and 10 uncertain variants in PRRT2 have source records linked to Seizures, benign familial infantile, 3. Association strength is not clinical gene validity.
Where Seizures, benign familial infantile, 3 variants cluster
- SCN2A S4 of repeat IV (positions 1624–1640): 16 of 167 ClinVar pathogenic / likely pathogenic variants, 11.3× more than its size predicts.
- KCNQ2 Mediates interaction with SLC5A3/SMIT1 (positions 222–323): 20 of 57 ClinVar pathogenic / likely pathogenic variants, 3.0× more than its size predicts.
- KCNQ2 Segment S4 (positions 197–215): 8 of 57 ClinVar pathogenic / likely pathogenic variants, 6.4× more than its size predicts.
- SCN8A S4 of repeat I (positions 218–234): 3 of 12 ClinVar pathogenic / likely pathogenic variants, 29.1× more than its size predicts.
- SCN2A Extracellular (positions 209–214): 5 of 167 ClinVar pathogenic / likely pathogenic variants, 10.0× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Seizures, benign familial infantile, 3
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| KCNQ2 A185T | 185 | Extracellular | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A185S | 185 | Extracellular | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R213L | 213 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R213Q | 213 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| SCN2A R937H | 937 | II | Pathogenic / likely pathogenic (★★) |
| SCN2A R1319Q | 1319 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A R1319W | 1319 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A M1490V | 1490 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A M1501T | 1501 | III | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A265V | 265 | Segment H5 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A265P | 265 | Segment H5 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A265G | 265 | Segment H5 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A294E | 294 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A294G | 294 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ3 R230C | 230 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| KCNQ3 R330C | 330 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ3 R364H | 364 | Mediates interaction with calmodulin | Pathogenic / likely pathogenic (★★) |
| SCN2A A240T | 240 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A A240S | 240 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A A263V | 263 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A V423L | 423 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A V424A | 424 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A V424M | 424 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A L979W | 979 | II | Pathogenic / likely pathogenic (★★) |
| SCN2A R1319P | 1319 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A A1333T | 1333 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A M1545V | 1545 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A V1627M | 1627 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A R1629C | 1629 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A R1629H | 1629 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A I1636M | 1636 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A I1640F | 1640 | IV | Pathogenic / likely pathogenic (★★) |
| SCN2A R1882Q | 1882 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| SCN2A R1882G | 1882 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ2 V182M | 182 | Segment S3 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R207W | 207 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R210C | 210 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 G256W | 256 | Mediates interaction with SLC5A3/SMIT1 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A294S | 294 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A306V | 306 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R333W | 333 | Mediates interaction with calmodulin | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R547W | 547 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ2 M578V | 578 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| SCN2A R223Q | 223 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A V261M | 261 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A R856Q | 856 | II | Pathogenic / likely pathogenic (★★) |
| SCN2A G899S | 899 | II | Pathogenic / likely pathogenic (★★) |
| SCN2A N1475K | 1475 | III | Pathogenic / likely pathogenic (★★) |
| SCN2A R1635Q | 1635 | IV | Pathogenic / likely pathogenic (★★) |
| SCN8A R850Q | 850 | II | Pathogenic / likely pathogenic (★★) |
| KCNQ2 S195C | 195 | Extracellular | Pathogenic / likely pathogenic (★★) |
| KCNQ2 T217I | 217 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ2 A306P | 306 | Segment S6 | Pathogenic / likely pathogenic (★★) |
| KCNQ2 N350K | 350 | Mediates interaction with calmodulin | Pathogenic / likely pathogenic (★★) |
| KCNQ2 R353C | 353 | Mediates interaction with calmodulin | Pathogenic / likely pathogenic (★★) |
| SCN2A L210Q | 210 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A V213A | 213 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A L216W | 216 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A L241R | 241 | I | Pathogenic / likely pathogenic (★★) |
| SCN2A Q383E | 383 | I | Pathogenic / likely pathogenic (★★) |
Showing 60 of 247.
Uncertain variants prioritized for review in Seizures, benign familial infantile, 3
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| SCN2A M1501I | 1501 | III | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; M1501T at the same position is pathogenic; REVEL 0.828 |
| SCN2A M1354V | 1354 | III | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; M1354T at the same position is pathogenic; REVEL 0.929 |
Which prediction tools work for Seizures, benign familial infantile, 3
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 94 out of 100
- MetaLR: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- ESM1b (LLR): 91 out of 100
- CADD: 91 out of 100
- MutPred2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 84 out of 100
- PolyPhen-2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 77 out of 100
- phyloP: 63 out of 100
Same protein, different disease
- Complex neurodevelopmental disorder also has ClinVar records linked to SCN2A variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (22 pathogenic / likely pathogenic).
- Episodic ataxia type 2 also has ClinVar records linked to SCN2A variants; they fall in the same places as the Seizures, benign familial infantile, 3 variants (15 pathogenic / likely pathogenic).
- Infantile spasms also has ClinVar records linked to SCN2A variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (14 pathogenic / likely pathogenic).
- Benign familial infantile epilepsy also has ClinVar records linked to SCN2A variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (6 pathogenic / likely pathogenic).
- Early-infantile DEE also has ClinVar records linked to KCNQ2 variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (199 pathogenic / likely pathogenic).
- Early-infantile DEE also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Seizures, benign familial infantile, 3 variants (90 pathogenic / likely pathogenic).
- Cognitive impairment with or without cerebellar ataxia also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Seizures, benign familial infantile, 3 variants (22 pathogenic / likely pathogenic).
- Complex neurodevelopmental disorder also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Seizures, benign familial infantile, 3 variants (8 pathogenic / likely pathogenic).
- Autosomal recessive inheritance also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Seizures, benign familial infantile, 3 variants (3 pathogenic / likely pathogenic).
- Myoclonus, familial, 2 also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Seizures, benign familial infantile, 3 variants (3 pathogenic / likely pathogenic).
- Benign neonatal seizures also has ClinVar records linked to KCNQ3 variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (13 pathogenic / likely pathogenic).
- Episodic kinesigenic dyskinesia also has ClinVar records linked to PRRT2 variants; they fall partly in the same places as the Seizures, benign familial infantile, 3 variants (8 pathogenic / likely pathogenic).
Diseases related to Seizures, benign familial infantile, 3
- Epilepsy, also linked to KCNQ2, KCNQ3, SCN2A and SCN8A
- Infantile spasms, also linked to KCNQ2, SCN2A and SCN8A
- Genetic developmental and epileptic encephalopathy, also linked to KCNQ2, SCN2A and SCN8A
- Early-infantile DEE, also linked to KCNQ2 and SCN8A
- Amyotrophic lateral sclerosis, also linked to SCN2A and SCN8A
- Cardiac arrhythmia, also linked to SCN2A and SCN8A
- Complex neurodevelopmental disorder, also linked to SCN2A and SCN8A
- Benign neonatal seizures, also linked to KCNQ2 and KCNQ3
- Rolandic epilepsy, also linked to KCNQ3 and SCN2A
- Benign familial infantile epilepsy, also linked to PRRT2 and SCN2A
- Focal epilepsy, also linked to SCN2A and SCN8A
- Migraine, also linked to SCN2A and SCN8A
Frequently asked questions
Which genes have records linked to Seizures, benign familial infantile, 3?
This view contains 5 analyzed proteins: SCN2A, KCNQ2, SCN8A, KCNQ3, PRRT2. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 247 pathogenic or likely pathogenic variants, 675 variants of uncertain significance and 119 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 2 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 1,084 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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