Is CHRNB2 c.210+9A>G pathogenic?

CHRNB2 c.210+9A>G is classified Benign in CHRNB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 35.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 c.210+9A>G?

CHRNB2 c.210+9A>G 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 c.210+9A>G

Q: How common is CHRNB2 c.210+9A>G in the general population?

CHRNB2 c.210+9A>G is common (popmax 35.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs3926124 · VCV158333

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 35.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -4
Non-coding constraint	Z 2.13	1 kb window · o/e 0.79 · regional · uncalibrated
Overall
CADD	6.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.8% African / African-American · 26,841/74,922 alleles

Filtering AF 35.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.3%

Overall 1.88% 30,311/1,613,970 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35.8%	3
Remaining individualsnot grpmax-eligible	2.34%	43
Middle Eastern	2.1%	48
Admixed American	2.08%	48
South Asian	0.155%	646
European (non-Finnish)	0.041%	2,438
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Finnishnot grpmax-eligible	0.00469%	21,323

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.210+9A>G
MANE Select: NM_000748
dbSNP: rs3926124
Type: single nucleotide variant
Location: chr1:154569616 (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-210-plus-9a-g (accessed [today's date]).

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