Febrile seizures, familial, 3a: genes and variants
Explore variant evidence for Febrile seizures, familial, 3a across 2 analyzed proteins (GABRG2, SCN1A). Linked ClinVar records include 31 pathogenic or likely pathogenic variants, 169 variants of uncertain significance and 25 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.
Download variant evidence (CSV)
Genes linked to Febrile seizures, familial, 3a
GABRG2: Gamma-aminobutyric acid receptor subunit gamma-2
The gene product supplies the gamma-2 subunit of synaptic GABA-A receptors, which are pentameric chloride channels activated by the inhibitory neurotransmitter GABA. The subunit helps receptor assembly and localization at neuronal membranes, and GABRG2 variants are associated with several epilepsy syndromes.
31 ClinVar pathogenic / likely pathogenic and 193 uncertain variants in GABRG2 have source records linked to Febrile seizures, familial, 3a. Association strength is not clinical gene validity.
SCN1A: Sodium channel protein type 1 subunit alpha
Its sodium current is especially important for reliable firing of inhibitory interneurons and therefore for balancing excitation across neural networks. Loss-of-function variants are the major cause of Dravet syndrome, while other variants cause GEFS+ or familial hemiplegic migraine.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN1A have source records linked to Febrile seizures, familial, 3a. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): SCN9A.
Where Febrile seizures, familial, 3a variants cluster
- GABRG2 Transmembrane (positions 303–322): 7 of 31 ClinVar pathogenic / likely pathogenic variants, 5.4× more than its size predicts.
- GABRG2 Extracellular (positions 323–334): 5 of 31 ClinVar pathogenic / likely pathogenic variants, 6.4× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Febrile seizures, familial, 3a
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GABRG2 R82Q | 82 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 T310I | 310 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| GABRG2 R323W | 323 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 R82W | 82 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 S325L | 325 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 N167K | 167 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 P282S | 282 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| GABRG2 V287I | 287 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| GABRG2 G354V | 354 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| GABRG2 R363W | 363 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| GABRG2 T90M | 90 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 A106T | 106 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 G257R | 257 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 N72K | 72 | Extracellular | Pathogenic / likely pathogenic (★★) |
| GABRG2 R82L | 82 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 T310S | 310 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 R323G | 323 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 P83L | 83 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 A300T | 300 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| GABRG2 A303T | 303 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 S306F | 306 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 T314S | 314 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 I321T | 321 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 T311A | 311 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GABRG2 R363G | 363 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| GABRG2 T112P | 112 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 R125H | 125 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 T181S | 181 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 A334V | 334 | Extracellular | Pathogenic / likely pathogenic (★) |
| GABRG2 R177G | 177 | Extracellular | Pathogenic / likely pathogenic |
| GABRG2 K328M | 328 | Extracellular | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Febrile seizures, familial, 3a
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| GABRG2 P83T | 83 | Extracellular | Conflicting reports (★) | +6: 4 other pathogenic changes within 3 positions; P83L at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| GABRG2 A300D | 300 | Cytoplasmic | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; A300T at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
Which prediction tools work for Febrile seizures, familial, 3a
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MutPred2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 93 out of 100
- EVE: 91 out of 100
- PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 81 out of 100
- SIFT: 81 out of 100
- CATVariant: 79 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 70 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 59 out of 100
Diseases related to Febrile seizures, familial, 3a
- Generalized epilepsy with febrile seizures plus, also linked to GABRG2 and SCN1A
- Epilepsy, also linked to GABRG2 and SCN1A
- Migraine, also linked to GABRG2 and SCN1A
- Genetic developmental and epileptic encephalopathy, also linked to GABRG2 and SCN1A
- Lennox-Gastaut syndrome, also linked to GABRG2 and SCN1A
- Early-infantile DEE, also linked to SCN1A
- Severe myoclonic epilepsy in infancy, also linked to SCN1A
- Amyotrophic lateral sclerosis, also linked to SCN1A
- Cardiac arrhythmia, also linked to SCN1A
- EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2, also linked to GABRG2
- Migraine, familial hemiplegic, 1, also linked to SCN1A
- Rolandic epilepsy, also linked to GABRG2
Frequently asked questions
Which genes have records linked to Febrile seizures, familial, 3a?
This view contains 2 analyzed proteins: GABRG2, SCN1A. 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 31 pathogenic or likely pathogenic variants, 169 variants of uncertain significance and 25 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 233 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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