Is CHRNA2 p.Arg262fs (c.784del) pathogenic?

CHRNA2 p.Arg262fs (c.784del) is classified Uncertain significance in CHRNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-09). Very rare (popmax 0.00133%, afr); Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNA2 p.Arg262fs (c.784del)?

CHRNA2 p.Arg262fs (c.784del) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNA2 p.Arg262fs (c.784del) in the general population?

CHRNA2 p.Arg262fs (c.784del) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNA2 p.Arg262fs

c.784del · rs1332347946 · VCV1026732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,994 alleles

Overall 0.000205% 3/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-Americangrpmax	0.00133%	74,994

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHRNA2
Protein: p.Arg262fs
Coding: c.784del
MANE Select: NM_000742
dbSNP: rs1332347946
Type: Deletion
Location: chr8:27463659 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 1 PDB

Full CHRNA2 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

CHRNA2 p.Arg262Trp Uncertain significance ★★ ⚠ same residue
CHRNA2 p.Glu420fs Uncertain significance ★★ same condition
CHRNA2 p.Ile500del Uncertain significance ★★ same condition
CHRNA2 p.Leu41fs Uncertain significance ★★ same condition
CHRNA2 p.Lys162fs Uncertain significance ★★ same condition
CHRNA2 p.Pro385fs Uncertain significance ★★ same condition
CHRNA2 p.Val135fs Uncertain significance ★★ same condition
CHRNA2 c.1464+7_1464+8del Likely benign ★★ 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/chrna2-p-arg262fs (accessed [today's date]).

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