Is CHRNB1 p.Asp112= (c.336C>T) pathogenic?

CHRNB1 p.Asp112= (c.336C>T) is classified Likely benign in CHRNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). Very rare (popmax 0.00174%, amr); Associated with congenital myasthenic syndrome 2A.

What condition is associated with CHRNB1 p.Asp112= (c.336C>T)?

CHRNB1 p.Asp112= (c.336C>T) is associated with congenital myasthenic syndrome 2A (ClinVar).

How common is CHRNB1 p.Asp112= (c.336C>T) in the general population?

CHRNB1 p.Asp112= (c.336C>T) is very rare (popmax 0.00174%, amr) (gnomAD).

CHRNB1 p.Asp112=

c.336C>T · rs1908657893 · VCV2426868

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00174%, amr)

Conditions

congenital myasthenic syndrome 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.6	GERP -5.1
Overall
CADD	2.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% Admixed American · 1/57,418 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000452% 7/1,548,654 alleles · very rare exomes 5/1,402,194 · genomes 2/146,460 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00174%	57,418
South Asian	0.00111%	89,748
European (non-Finnish)	0.000438%	228,343

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: CHRNB1
Protein: p.Asp112=
Coding: c.336C>T
MANE Select: NM_000747
dbSNP: rs1908657893
Type: single nucleotide variant
Location: chr17:7446925 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 25 PDB

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.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
CHRNB1 p.Ala18Gly 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-asp112 (accessed [today's date]).

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