Is CHRNB1 p.Ser438= (c.1314C>T) pathogenic?

CHRNB1 p.Ser438= (c.1314C>T) is classified Likely benign in CHRNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 2A.

What condition is associated with CHRNB1 p.Ser438= (c.1314C>T)?

CHRNB1 p.Ser438= (c.1314C>T) is associated with congenital myasthenic syndrome 2A (ClinVar).

How common is CHRNB1 p.Ser438= (c.1314C>T) in the general population?

CHRNB1 p.Ser438= (c.1314C>T) is absent from gnomAD v4.1 (gnomAD).

CHRNB1 p.Ser438=

c.1314C>T · rs576092367 · VCV756157

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myasthenic syndrome 2A

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 0.57	GERP -4.7, phastCons 1
Overall
CADD	6.77	PHRED · no single calibrated threshold — expert panels disagree

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: CHRNB1
Protein: p.Ser438=
Coding: c.1314C>T
MANE Select: NM_000747
dbSNP: rs576092367
Type: single nucleotide variant
Location: chr17:7455890 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 25 PDB
Residue 438: an α-helix

Full CHRNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNB1 p.Ser438Phe Uncertain significance ★ ⚠ same residue
CHRNB1 p.Arg243Cys Pathogenic/Likely pathogenic ★★ same condition
CHRNB1 p.Glu275Ter Pathogenic/Likely pathogenic ★★ same condition
CHRNB1 p.Val289Met Pathogenic ★★ ⚠ same condition
CHRNB1 c.1218-3C>T Uncertain significance ★★ same condition
CHRNB1 c.1365+5G>C Uncertain significance ★★ same condition
CHRNB1 p.Ala105Val Uncertain significance ★★ ⚠ same condition
CHRNB1 p.Ala15Val 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/chrnb1-p-ser438 (accessed [today's date]).

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