Is CHRNA2 p.Ser203= (c.609C>T) pathogenic?

CHRNA2 p.Ser203= (c.609C>T) is classified Likely benign in CHRNA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-29). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHRNA2 p.Ser203= (c.609C>T)?

CHRNA2 p.Ser203= (c.609C>T) is associated with Inborn genetic diseases, familial sleep-related hypermotor epilepsy (ClinVar).

How common is CHRNA2 p.Ser203= (c.609C>T) in the general population?

CHRNA2 p.Ser203= (c.609C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

CHRNA2 p.Ser203=

c.609C>T · rs761237311 · VCV388535

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

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 1.8	GERP -0.14, phastCons 1
Overall
CADD	9.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
European (non-Finnish)	0.00119%	84,287

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.Ser203=
Coding: c.609C>T
MANE Select: NM_000742
dbSNP: rs761237311
Type: single nucleotide variant
Location: chr8:27463834 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 1 PDB
Residue 203: a β-strand

Full CHRNA2 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

CHRNA2 p.Ser203fs Conflicting classifications of pathogenicity ★ 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-ser203 (accessed [today's date]).

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