Is SCN2A p.Leu796= (c.2388G>C) pathogenic?

SCN2A p.Leu796= (c.2388G>C) is classified Uncertain significance in SCN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-31). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 11.

What condition is associated with SCN2A p.Leu796= (c.2388G>C)?

SCN2A p.Leu796= (c.2388G>C) is associated with developmental and epileptic encephalopathy, 11, seizures, benign familial infantile, 3 (ClinVar).

How common is SCN2A p.Leu796= (c.2388G>C) in the general population?

SCN2A p.Leu796= (c.2388G>C) is absent from gnomAD v4.1 (gnomAD).

SCN2A p.Leu796=

c.2388G>C · rs2105293632 · VCV1496289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.50	donor loss · deltas
Pangolin	Δ0.25	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	20.3	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: SCN2A
Protein: p.Leu796=
Coding: c.2388G>C
MANE Select: NM_001040142
dbSNP: rs2105293632
Type: single nucleotide variant
Location: chr2:165331568 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 5 PDB
Residue 796: 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); an α-helix

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

Disease context

developmental and epileptic encephalopathy, 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: seizures, benign familial infantile, 3

Similar variants

SCN2A p.Ala1773Thr Pathogenic ★★★ same condition
SCN2A p.Arg220Gly Likely pathogenic ★★★ same condition
SCN2A p.Arg853Gln Pathogenic ★★★ same condition
SCN2A p.Gly899Asp Likely pathogenic ★★★ same condition
SCN2A p.Leu1611Pro Pathogenic ★★★ same condition
SCN2A p.Leu886Ser Likely pathogenic ★★★ same condition
SCN2A p.Lys1260Glu Likely pathogenic ★★★ same condition
SCN2A p.Lys156Gln 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/scn2a-p-leu796 (accessed [today's date]).

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