Is SCN2A p.Arg607fs (c.1819_1831del) pathogenic?

SCN2A p.Arg607fs (c.18191831del) is classified Pathogenic in SCN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-05). Absent from gnomAD; Associated with seizures, benign familial infantile, 3.

What condition is associated with SCN2A p.Arg607fs (c.1819_1831del)?

SCN2A p.Arg607fs (c.1819_1831del) is associated with seizures, benign familial infantile, 3, developmental and epileptic encephalopathy, 11 (ClinVar).

How common is SCN2A p.Arg607fs (c.1819_1831del) in the general population?

SCN2A p.Arg607fs (c.1819_1831del) is absent from gnomAD (gnomAD).

How is Self-limited neonatal-infantile epilepsy inherited?

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

SCN2A p.Arg607fs

c.1819_1831del · rs2105276912 · VCV1365870

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

seizures, benign familial infantile, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCN2A
Protein: p.Arg607fs
Coding: c.1819_1831del
MANE Select: NM_001040142
dbSNP: rs2105276912
Type: Deletion
Location: chr2:165323302 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 5 PDB
Residue 607: a UniProt-annotated variant site (found in a patient with intractable epilepsy and severe mental decline; likely pathogenic; non-conducting; loss of voltage-gated sodium channel activity; dominant-negative); a UniProt-annotated variant site (found in a patient with schizofrenia; uncertain significance); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic); the 'disordered' region

Full SCN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

seizures, benign familial infantile, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 11

For Self-limited neonatal-infantile epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

SCN2A p.Arg607Ter Pathogenic ★★ same residue
SCN2A p.Arg607Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
SCN2A p.Leu577fs Pathogenic ★★ same condition
SCN2A p.Phe1661fs Pathogenic/Likely pathogenic ★★ same condition
SCN2A p.Ser484fs Pathogenic ★★ same condition
SCN2A c.605+4_605+7del Uncertain significance ★★ same condition
SCN2A p.Glu1956_Asn1957del Uncertain significance ★★ same condition
SCN2A p.Lys1946del Uncertain significance ★★ 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/scn2a-p-arg607fs (accessed [today's date]).

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