Is SCN8A p.Val960Asp (c.2879T>A) pathogenic?

SCN8A p.Val960Asp (c.2879T>A) is classified Pathogenic in SCN8A (ClinVar, Single submitter, 2 submitters; last evaluated 2019-07-29). AlphaMissense: likely pathogenic (0.9942); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 13.

What condition is associated with SCN8A p.Val960Asp (c.2879T>A)?

SCN8A p.Val960Asp (c.2879T>A) is associated with developmental and epileptic encephalopathy, 13 (ClinVar).

How common is SCN8A p.Val960Asp (c.2879T>A) in the general population?

SCN8A p.Val960Asp (c.2879T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCN8A p.Val960Asp (c.2879T>A)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

SCN8A p.Val960Asp

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.2879T>A · rs879255703 · VCV253287

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9942 · 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	0.9942	likely pathogenic ✓ concordant with ClinVar
REVEL	0.989	strongly pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 17 kb · p 8.5e-44 · regional, not allelic
Overall
CADD	27.5	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.Val960Asp
Coding: c.2879T>A
MANE Select: NM_001330260
dbSNP: rs879255703
Type: single nucleotide variant
Location: chr12:51766005 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.90 · 7 PDB
Residue 960: a UniProt-annotated variant site (in dee13; uncertain significance); 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.Val960Phe Uncertain significance ★ ⚠ same residue
SCN8A p.Val960= Likely benign ★ 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

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-val960asp (accessed [today's date]).

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