CHRNE p.Arg435=
c.1303A>C · rs1486674648 · VCV1132294
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
congenital myasthenic syndrome 4A
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 · T>A here scores Δ0.32 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -3.5, phastCons 0.9 |
| Overall | ||
| CADD | 6.858 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,766 alleles
Overall
0.000124%
2/1,608,610 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,766 |
| African / African-American | 0.00134% | 74,878 |
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
- CHRNE
- Protein
- p.Arg435=
- Coding
- c.1303A>C
- MANE Select
- NM_000080
- dbSNP
- rs1486674648
- Type
- single nucleotide variant
- Location
- chr17:4899024 (GRCh38)
- Gene constraint
- LOEUF 1.298 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 25 PDB
- Residue 435
- an α-helix
Similar variants
- CHRNE c.1032+1G>A Likely pathogenic ★★ same condition
- CHRNE c.1033-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CHRNE c.1033-2A>T Pathogenic/Likely pathogenic ★★ same condition
- CHRNE c.1219+2T>G Pathogenic ★★ same condition
- CHRNE c.1220-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CHRNE c.1220-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CHRNE c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHRNE c.345-2A>G Pathogenic/Likely pathogenic ★★ 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/chrne-p-arg435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown