Is CHRNB2 p.His71Gln (c.213T>G) pathogenic?

CHRNB2 p.His71Gln (c.213T>G) is classified Likely benign in CHRNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: ambiguous (0.3406); Very rare (popmax 0.00178%, nfe); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNB2 p.His71Gln (c.213T>G)?

CHRNB2 p.His71Gln (c.213T>G) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 p.His71Gln (c.213T>G) in the general population?

CHRNB2 p.His71Gln (c.213T>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

What do computational predictors say about CHRNB2 p.His71Gln (c.213T>G)?

AlphaMissense predicts ambiguous (score 0.3406) — an in-silico prediction, not a clinical call.

CHRNB2 p.His71Gln

c.213T>G · rs763194096 · VCV833563

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3406 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
AlphaMissense	0.3406	ambiguous
REVEL	0.44	indeterminate
SaProt	LLR -6.44	tolerated
Splicing
SpliceAI	Δ0.91	acceptor gain · deltas
Pangolin	Δ0.62	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -10	GERP -3.7
Regional constraint	o/e 0.74	unconstrained · MANE · 3,773 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	18.13	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,024 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,614,040 alleles · very rare

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
Protein: p.His71Gln
Coding: c.213T>G
MANE Select: NM_000748
dbSNP: rs763194096
Type: single nucleotide variant
Location: chr1:154569794 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB
Residue 71: a β-strand

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.His71Arg 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 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-his71gln (accessed [today's date]).

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