Is CHRNB1 p.Arg29Pro (c.86G>C) pathogenic?

CHRNB1 p.Arg29Pro (c.86G>C) is classified Uncertain significance in CHRNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). AlphaMissense: ambiguous (0.4171); Ultra-rare (popmax 0.0167%, amr); Associated with congenital myasthenic syndrome 2A.

What condition is associated with CHRNB1 p.Arg29Pro (c.86G>C)?

CHRNB1 p.Arg29Pro (c.86G>C) is associated with congenital myasthenic syndrome 2A (ClinVar).

How common is CHRNB1 p.Arg29Pro (c.86G>C) in the general population?

CHRNB1 p.Arg29Pro (c.86G>C) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about CHRNB1 p.Arg29Pro (c.86G>C)?

AlphaMissense predicts ambiguous (score 0.4171) — an in-silico prediction, not a clinical call.

CHRNB1 p.Arg29Pro

c.86G>C · rs767799511 · VCV1428635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

congenital myasthenic syndrome 2A

Computational evidence

Protein change
AlphaMissense	0.4171	ambiguous
REVEL	0.596	indeterminate
SaProt	LLR -17.31	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.2, phastCons 0.97
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.051 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.0167% Admixed American · 10/59,958 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00062% 10/1,612,594 alleles · ultra-rare exomes 9/1,460,370 · genomes 1/152,224 · joint denominator

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.Arg29Pro
Coding: c.86G>C
MANE Select: NM_000747
dbSNP: rs767799511
Type: single nucleotide variant
Location: chr17:7445297 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 25 PDB
Residue 29: 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.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-arg29pro (accessed [today's date]).

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