CHRNA1 p.Lys124=
c.372G>A · rs143047599 · VCV1117095
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
Conditions
1
lethal multiple pterygium syndrome
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 · C>A here scores Δ0.57 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 12.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/75,018 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00124%
20/1,614,078 alleles · ultra-rare
exomes 7/1,461,856 · genomes 13/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.024% | 4,168 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
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
- CHRNA1
- Protein
- p.Lys124=
- Coding
- c.372G>A
- MANE Select
- NM_000079
- dbSNP
- rs143047599
- Type
- single nucleotide variant
- Location
- chr2:174754387 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.34 · 27 PDB
Similar variants
- CHRNA1 p.Lys124Ter Pathogenic/Likely pathogenic ★★ same residue
- CHRNA1 p.Arg333Trp Pathogenic/Likely pathogenic ★★ same condition
- CHRNA1 p.Gln131Ter Pathogenic/Likely pathogenic ★★ same condition
- CHRNA1 p.Gln59Ter Pathogenic ★★ same condition
- CHRNA1 p.Gly173Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CHRNA1 p.Gly441Arg Pathogenic/Likely pathogenic ★★ same condition
- CHRNA1 c.*101C>T Uncertain significance ★★ same condition
- CHRNA1 p.Ala121Thr 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/chrna1-p-lys124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown