CHRNB1 p.Val463=
c.1389G>A · rs1283448996 · VCV760128
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
1
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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.33, phastCons 1 |
| Overall | ||
| CADD | 9.417 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,874 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,614,014 alleles · very rare
exomes 1/1,461,890 · genomes 3/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,874 |
| European (non-Finnish) | 0.000254% | 393,348 |
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.Val463=
- Coding
- c.1389G>A
- MANE Select
- NM_000747
- dbSNP
- rs1283448996
- Type
- single nucleotide variant
- Location
- chr17:7456606 (GRCh38)
- Gene constraint
- LOEUF 1.047 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.01 · 25 PDB
- Residue 463
- an α-helix
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-val463 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown