Is SCN8A p.Phe360Ser (c.1079T>C) pathogenic?

SCN8A p.Phe360Ser (c.1079T>C) is classified Likely pathogenic in SCN8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9932); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 13.

What condition is associated with SCN8A p.Phe360Ser (c.1079T>C)?

SCN8A p.Phe360Ser (c.1079T>C) is associated with developmental and epileptic encephalopathy, 13 (ClinVar).

How common is SCN8A p.Phe360Ser (c.1079T>C) in the general population?

SCN8A p.Phe360Ser (c.1079T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCN8A p.Phe360Ser (c.1079T>C)?

AlphaMissense predicts likely pathogenic (score 0.9932) — an in-silico prediction, not a clinical call.

SCN8A p.Phe360Ser

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1079T>C · VCV4277912

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 13

Computational evidence

Protein change
AlphaMissense	0.9932	likely pathogenic ✓ concordant with ClinVar
REVEL	0.974	strongly pathogenic-leaning
SaProt	LLR -16.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 4,449 bp · p 9.4e-24 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCN8A
Protein: p.Phe360Ser
Coding: c.1079T>C
MANE Select: NM_001330260
Type: single nucleotide variant
Location: chr12:51702859 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.90 · 7 PDB
Residue 360: an α-helix

Full SCN8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

SCN8A p.Phe360Leu Uncertain significance ★ ⚠ same residue
SCN8A p.Arg1872Gln Pathogenic ★★★ ⚠ same condition
SCN8A p.Asn1318Ser Likely pathogenic ★★★ same condition
SCN8A p.Ser845Phe Likely pathogenic ★★★ ⚠ same condition
SCN8A p.Ala1323Ser Pathogenic/Likely pathogenic ★★ same condition
SCN8A p.Ala1323Thr Pathogenic/Likely pathogenic ★★ same condition
SCN8A p.Ala1650Thr Pathogenic ★★ same condition
SCN8A p.Ala874Thr Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/scn8a-p-phe360ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown