Is CHRNB2 p.Val287= (c.861G>T) pathogenic?

CHRNB2 p.Val287= (c.861G>T) is classified Likely benign in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-19). Absent from gnomAD v4.1; Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 p.Val287= (c.861G>T)?

CHRNB2 p.Val287= (c.861G>T) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 p.Val287= (c.861G>T) in the general population?

CHRNB2 p.Val287= (c.861G>T) is absent from gnomAD v4.1 (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNB2 p.Val287=

c.861G>T · VCV3689829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial sleep-related hypermotor epilepsy

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 2.8	GERP 0.91, phastCons 1
Overall
CADD	9.365	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: CHRNB2
Protein: p.Val287=
Coding: c.861G>T
MANE Select: NM_000748
Type: single nucleotide variant
Location: chr1:154571684 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB
Residue 287: a UniProt-annotated variant site (in enfl3); a UniProt-annotated variant site (in enfl3; approximately 10-fold increase in acetylcholine sensitivity)

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.Val287Leu Pathogenic/Likely pathogenic ★★ same residue
CHRNB2 p.Val287Met Pathogenic ★★ same residue
CHRNB2 p.Val287_Pro289del Uncertain significance ★★ same residue
CHRNB2 p.Val308Ala Pathogenic/Likely pathogenic ★★ same condition
CHRNB2 c.1338+3G>T Uncertain significance ★★ same condition
CHRNB2 c.366-3C>T Uncertain significance ★★ same condition
CHRNB2 p.Ala135Val Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Ala154Thr 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-val287 (accessed [today's date]).

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