Is CHRNB2 p.Phe378del (c.1129TTC[1]) pathogenic?

CHRNB2 p.Phe378del (c.1129TTC[1]) is classified Uncertain significance in CHRNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-22). Absent from gnomAD; Associated with autosomal dominant nocturnal frontal lobe epilepsy 3.

What condition is associated with CHRNB2 p.Phe378del (c.1129TTC[1])?

CHRNB2 p.Phe378del (c.1129TTC[1]) is associated with autosomal dominant nocturnal frontal lobe epilepsy 3 (ClinVar).

How common is CHRNB2 p.Phe378del (c.1129TTC[1]) in the general population?

CHRNB2 p.Phe378del (c.1129TTC[1]) is absent from gnomAD (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNB2 p.Phe378del

c.1129TTC[1] · rs796052330 · VCV205078

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal dominant nocturnal frontal lobe epilepsy 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · substitutions only

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: CHRNB2
Protein: p.Phe378del
Coding: c.1129TTC[1]
MANE Select: NM_000748
dbSNP: rs796052330
Type: Microsatellite
Location: chr1:154571950 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB

Full CHRNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nocturnal frontal lobe epilepsy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sleep-related hypermotor epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CHRNB2 p.Asn122del Conflicting classifications of pathogenicity ★ same condition
CHRNB2 p.Phe378Ser Uncertain significance ★ ⚠ same residue
CHRNB2 p.Val287Leu Pathogenic/Likely pathogenic ★★ same condition
CHRNB2 p.Val287Met Pathogenic ★★ same condition
CHRNB2 p.Val308Ala Pathogenic/Likely pathogenic ★★ same condition
CHRNB2 c.1338+3G>T Uncertain significance ★★ same condition
CHRNB2 p.Arg106Gln Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Arg232Cys 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/chrnb2-p-phe378del (accessed [today's date]).

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