Is CHRNB2 p.Arg362Cys (c.1084C>T) pathogenic?

CHRNB2 p.Arg362Cys (c.1084C>T) is classified Conflicting classifications of pathogenicity in CHRNB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2488); Ultra-rare (popmax 0.0337%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHRNB2 p.Arg362Cys (c.1084C>T)?

CHRNB2 p.Arg362Cys (c.1084C>T) is associated with Inborn genetic diseases, familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNB2 p.Arg362Cys (c.1084C>T) in the general population?

CHRNB2 p.Arg362Cys (c.1084C>T) is ultra-rare (popmax 0.0337%, afr) (gnomAD).

What do computational predictors say about CHRNB2 p.Arg362Cys (c.1084C>T)?

AlphaMissense predicts likely benign (score 0.2488) — an in-silico prediction, not a clinical call.

CHRNB2 p.Arg362Cys

c.1084C>T · rs199928622 · VCV1017968

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2488 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2488	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 4,110 bp · p 0.17 · regional, not allelic
Overall
CADD	24.4	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 0.0337% African / African-American · 25/74,184 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.02%

Overall 0.00171% 27/1,575,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0337%	2,967
Admixed American	0.0018%	55,494
Remaining individualsnot grpmax-eligible	0.00163%	61,296

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.Arg362Cys
Coding: c.1084C>T
MANE Select: NM_000748
dbSNP: rs199928622
Type: single nucleotide variant
Location: chr1:154571907 (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

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-arg362cys (accessed [today's date]).

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