Is CHRNB2 c.255+7G>C pathogenic?

CHRNB2 c.255+7G>C is classified Benign/Likely benign in CHRNB2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Rare (popmax 0.952%, amr); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 c.255+7G>C?

CHRNB2 c.255+7G>C is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 c.255+7G>C in the general population?

CHRNB2 c.255+7G>C is rare (popmax 0.952%, amr) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNB2 c.255+7G>C

rs190374968 · VCV136769

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.952%, amr)

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	Δ0.46	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -5.5	GERP -2.2, phastCons 0.037
Non-coding constraint	Z 2.13	1 kb window · o/e 0.79 · regional · uncalibrated
Overall
CADD	1.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.952% Admixed American · 571/60,004 alleles

Filtering AF 0.887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.861%

Overall 0.0361% 582/1,613,998 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.952%	105
Remaining individualsnot grpmax-eligible	0.008%	12,499
African / African-American	0.00533%	18,753
European (non-Finnish)	0.000169%	589,977

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHRNB2
Coding: c.255+7G>C
MANE Select: NM_000748
dbSNP: rs190374968
Type: single nucleotide variant
Location: chr1:154569843 (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.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 c.366-3C>T Uncertain significance ★★ same condition
CHRNB2 p.Ala135Val Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Ala154Thr Uncertain significance ★★ ⚠ same condition
CHRNB2 p.Ala207Gly 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-c-255-plus-7g-c (accessed [today's date]).

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