Is CHRNA2 p.Arg87Ser (c.259C>A) pathogenic?

CHRNA2 p.Arg87Ser (c.259C>A) is classified Uncertain significance in CHRNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-09). AlphaMissense: ambiguous (0.3447); Absent from gnomAD v4.1; Associated with benign familial infantile epilepsy.

What condition is associated with CHRNA2 p.Arg87Ser (c.259C>A)?

CHRNA2 p.Arg87Ser (c.259C>A) is associated with benign familial infantile epilepsy (ClinVar).

How common is CHRNA2 p.Arg87Ser (c.259C>A) in the general population?

CHRNA2 p.Arg87Ser (c.259C>A) is absent from gnomAD v4.1 (gnomAD).

How is Self-limited infantile epilepsy inherited?

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

What do computational predictors say about CHRNA2 p.Arg87Ser (c.259C>A)?

AlphaMissense predicts ambiguous (score 0.3447) — an in-silico prediction, not a clinical call.

CHRNA2 p.Arg87Ser

c.259C>A · VCV3779075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

benign familial infantile epilepsy

Computational evidence

Protein change
AlphaMissense	0.3447	ambiguous
REVEL	0.364	indeterminate
SaProt	LLR -9.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,404 bp · p 0.095 · regional, not allelic
Overall
CADD	25.8	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.Arg87Ser
Coding: c.259C>A
MANE Select: NM_000742
Type: single nucleotide variant
Location: chr8:27469796 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 1 PDB
Residue 87: a β-strand

Full CHRNA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

benign familial infantile epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Self-limited infantile epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

CHRNA2 p.Arg87His Uncertain significance ★★ ⚠ same residue
CHRNA2 p.Arg87Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CHRNA2 p.Lys450Asn Uncertain significance ★★ ⚠ same condition
CHRNA2 c.1464+4C>T Uncertain significance ★★ same type
CHRNA2 c.1464+5G>A Uncertain significance ★★ same type
CHRNA2 c.294+1G>A Uncertain significance ★★ same type
CHRNA2 c.294+5G>A Uncertain significance ★★ same type
CHRNA2 c.449+3A>T Uncertain significance ★★ same type

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-arg87ser (accessed [today's date]).

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