CHRNA1 p.Ser288=
c.864C>T · VCV4750343
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00263%, nfe)
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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 8.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00263%
European (non-Finnish) · 31/1,179,992 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00192%
31/1,613,854 alleles · very rare
exomes 30/1,461,864 · genomes 1/151,990 · 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
- CHRNA1
- Protein
- p.Ser288=
- Coding
- c.864C>T
- MANE Select
- NM_000079
- Type
- single nucleotide variant
- Location
- chr2:174750084 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.34 · 27 PDB
- Residue 288
- a β-strand
Similar variants
- 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 p.Lys124Ter 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-ser288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown