Is SCN8A p.Ala342= (c.1026A>G) pathogenic?

SCN8A p.Ala342= (c.1026A>G) is classified Likely benign in SCN8A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). Absent from gnomAD v4.1; Associated with early-infantile DEE.

What condition is associated with SCN8A p.Ala342= (c.1026A>G)?

SCN8A p.Ala342= (c.1026A>G) is associated with early-infantile DEE (ClinVar).

How common is SCN8A p.Ala342= (c.1026A>G) in the general population?

SCN8A p.Ala342= (c.1026A>G) is absent from gnomAD v4.1 (gnomAD).

SCN8A p.Ala342=

c.1026A>G · rs2138742369 · VCV1665335

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

early-infantile DEE

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -3.7, phastCons 0.18
Overall
CADD	9.503	PHRED · no single calibrated threshold — expert panels disagree

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.Ala342=
Coding: c.1026A>G
MANE Select: NM_001330260
dbSNP: rs2138742369
Type: single nucleotide variant
Location: chr12:51702806 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.90 · 7 PDB

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

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN8A c.615-1G>A Pathogenic ★★★ same condition
SCN8A p.Arg1872Gln Pathogenic ★★★ ⚠ same condition
SCN8A p.Asn418Asp Likely pathogenic ★★★ same condition
SCN8A p.Glu1218Lys Pathogenic ★★★ same condition
SCN8A p.Ile1631Thr Likely pathogenic ★★★ same condition
SCN8A p.Ser845Cys Likely pathogenic ★★★ ⚠ same condition
SCN8A p.Ser845Phe Likely pathogenic ★★★ ⚠ same condition
SCN8A p.Tyr401His 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-ala342 (accessed [today's date]).

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