Is CHRNB2 p.Leu67= (c.201C>T) pathogenic?

CHRNB2 p.Leu67= (c.201C>T) is classified Likely benign in CHRNB2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHRNB2 p.Leu67= (c.201C>T)?

CHRNB2 p.Leu67= (c.201C>T) is associated with Inborn genetic diseases, familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 p.Leu67= (c.201C>T) in the general population?

CHRNB2 p.Leu67= (c.201C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

CHRNB2 p.Leu67=

c.201C>T · rs773706734 · VCV477013

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Inborn genetic diseases

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 0.068	GERP -2.7, phastCons 0.9
Overall
CADD	11.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,008 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00235% 38/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.00329%	30,357
European (non-Finnish)	0.0022%	45,385

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.Leu67=
Coding: c.201C>T
MANE Select: NM_000748
dbSNP: rs773706734
Type: single nucleotide variant
Location: chr1:154569598 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 15 PDB
Residue 67: a β-strand

Full CHRNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial sleep-related hypermotor epilepsy

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-p-leu67 (accessed [today's date]).

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