Is CHRNB1 p.Val252= (c.756C>T) pathogenic?

CHRNB1 p.Val252= (c.756C>T) is classified Likely benign in CHRNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). Very rare (popmax 0.00161%, nfe); Associated with congenital myasthenic syndrome 2A.

What condition is associated with CHRNB1 p.Val252= (c.756C>T)?

CHRNB1 p.Val252= (c.756C>T) is associated with congenital myasthenic syndrome 2A (ClinVar).

How common is CHRNB1 p.Val252= (c.756C>T) in the general population?

CHRNB1 p.Val252= (c.756C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

CHRNB1 p.Val252=

c.756C>T · rs754596731 · VCV703151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

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 2.6	GERP 2.5, phastCons 1
Overall
CADD	12.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,064 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,614,166 alleles · very rare exomes 19/1,461,892 · genomes 1/152,274 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,109
African / African-American	0.00133%	74,950

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.Val252=
Coding: c.756C>T
MANE Select: NM_000747
dbSNP: rs754596731
Type: single nucleotide variant
Location: chr17:7448724 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 25 PDB
Residue 252: 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.Val252Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
CHRNB1 p.Val252Phe Uncertain significance ★ ⚠ same residue
CHRNB1 p.Val252Asp 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

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-val252 (accessed [today's date]).

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