Is CHRNA2 p.Asp117= (c.351C>T) pathogenic?

CHRNA2 p.Asp117= (c.351C>T) is classified Benign in CHRNA2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 43.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNA2 p.Asp117= (c.351C>T)?

CHRNA2 p.Asp117= (c.351C>T) is associated with familial sleep-related hypermotor epilepsy, autosomal dominant nocturnal frontal lobe epilepsy 4 (ClinVar).

How is Sleep-related hypermotor epilepsy inherited?

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

CHRNA2 p.Asp117=

Q: How common is CHRNA2 p.Asp117= (c.351C>T) in the general population?

CHRNA2 p.Asp117= (c.351C>T) is common (popmax 43.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.351C>T · rs2565061 · VCV128738

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 43.4%, eas) — 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.92, phastCons 1
Overall
CADD	6.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.4% East Asian · 19,417/44,742 alleles

Filtering AF 42.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.7%

Overall 14.8% 237,047/1,605,228 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	43.4%	2
African / African-American	23%	4
Admixed American	19.3%	5
Finnishnot grpmax-eligible	16.4%	6
Remaining individualsnot grpmax-eligible	14.6%	7
European (non-Finnish)	13.2%	8
South Asian	13.1%	8
Amishnot grpmax-eligible	12.4%	8
Middle Eastern	7.04%	14
Ashkenazi Jewishnot grpmax-eligible	6.4%	16

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.Asp117=
Coding: c.351C>T
MANE Select: NM_000742
dbSNP: rs2565061
Type: single nucleotide variant
Location: chr8:27467327 (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

Also linked: autosomal dominant nocturnal frontal lobe epilepsy 4

For Sleep-related hypermotor epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CHRNA2 p.Asp117Gly Uncertain significance ★ same residue
CHRNA2 c.1464+4C>T Uncertain significance ★★ same condition
CHRNA2 c.1464+5G>A Uncertain significance ★★ same condition
CHRNA2 c.294+1G>A Uncertain significance ★★ same condition
CHRNA2 c.294+5G>A Uncertain significance ★★ same condition
CHRNA2 c.449+3A>T Uncertain significance ★★ same condition
CHRNA2 c.73+4A>C Uncertain significance ★★ same condition
CHRNA2 p.Ala177Pro 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/chrna2-p-asp117 (accessed [today's date]).

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