Is CHRNB2 p.Gly414fs (c.1235dup) pathogenic?

CHRNB2 p.Gly414fs (c.1235dup) is classified Uncertain significance in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 p.Gly414fs (c.1235dup)?

CHRNB2 p.Gly414fs (c.1235dup) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNB2 p.Gly414fs

c.1235dup · VCV4748723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -2.9

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

Variant & gene context

Gene: CHRNB2
Protein: p.Gly414fs
Coding: c.1235dup
MANE Select: NM_000748
Type: Duplication
Location: chr1:154572055 (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

familial sleep-related hypermotor epilepsy — 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.Gly414Arg Uncertain significance ★★ ⚠ same residue
CHRNB2 p.Gly414= Likely benign ★★ same residue
CHRNB2 p.Ile283fs Uncertain significance ★★ same condition
CHRNB2 p.361LR[3] Uncertain significance ★ same condition
CHRNB2 p.Ala408_Pro409insAla Uncertain significance ★ same condition
CHRNB2 p.Arg174fs Uncertain significance ★ same condition
CHRNB2 p.Arg366_Gln367insArg Uncertain significance ★ same condition
CHRNB2 p.Leu11fs 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-gly414fs (accessed [today's date]).

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