Is CHRNA2 p.Arg72Ser (c.214C>A) pathogenic?

CHRNA2 p.Arg72Ser (c.214C>A) is classified Likely benign in CHRNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely pathogenic (0.5723); Absent from gnomAD v4.1; Associated with familial sleep-related hypermotor epilepsy.

What condition is associated with CHRNA2 p.Arg72Ser (c.214C>A)?

CHRNA2 p.Arg72Ser (c.214C>A) is associated with familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNA2 p.Arg72Ser (c.214C>A) in the general population?

CHRNA2 p.Arg72Ser (c.214C>A) is absent from gnomAD v4.1 (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 CHRNA2 p.Arg72Ser (c.214C>A)?

AlphaMissense predicts likely pathogenic (score 0.5723) — an in-silico prediction, not a clinical call.

CHRNA2 p.Arg72Ser

c.214C>A · rs201890355 · VCV1982742

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5723 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial sleep-related hypermotor epilepsy

Computational evidence

Protein change
AlphaMissense	0.5723	likely pathogenic
REVEL	0.227	benign-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP -0.12, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,404 bp · p 0.095 · regional, not allelic
Overall
CADD	25.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHRNA2
Protein: p.Arg72Ser
Coding: c.214C>A
MANE Select: NM_000742
dbSNP: rs201890355
Type: single nucleotide variant
Location: chr8:27469841 (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.Arg72Leu Uncertain significance ★★ ⚠ same residue
CHRNA2 p.Arg72Cys Uncertain significance ★ ⚠ same residue
CHRNA2 p.Arg72His Conflicting classifications of pathogenicity ★ ⚠ same residue
CHRNA2 p.Arg72Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CHRNA2 p.Arg72= Likely benign ★ 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

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-arg72ser (accessed [today's date]).

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