CHRNE p.Pro340=
c.1020G>A · rs2507543479 · VCV2851064
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.52e-05%, nfe)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.04 | GERP -3.8, phastCons 0.4 |
| Overall | ||
| CADD | 6.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.52e-05%
European (non-Finnish) · 1/1,173,310 alleles
Overall
6.92e-05%
1/1,444,574 alleles · very rare
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.Pro340=
- Coding
- c.1020G>A
- MANE Select
- NM_000080
- dbSNP
- rs2507543479
- Type
- single nucleotide variant
- Location
- chr17:4899480 (GRCh38)
- Gene constraint
- LOEUF 1.298 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 25 PDB
- Residue 340
- an α-helix
Similar variants
- CHRNE p.Pro340Arg Uncertain significance ★★ ⚠ same residue
- CHRNE p.Pro340Gln Uncertain significance ★★ ⚠ same residue
- CHRNE p.Pro340Ser Uncertain significance ★★ ⚠ same residue
- CHRNE p.Pro340Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro340 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown