Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 29.7%, sas) — too common for a highly-penetrant pathogenic allele
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 0.61 | GERP 0.81, phastCons 0.99 |
| Overall | ||
| CADD | 9.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
29.7%
South Asian · 20,028/67,450 alleles
Filtering AF
29.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 29.2%
Overall
19.9%
258,741/1,298,382 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 29.7% | 3 |
| Amishnot grpmax-eligible | 25.2% | 4 |
| Middle Eastern | 23.7% | 4 |
| Finnishnot grpmax-eligible | 22.3% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 20.6% | 5 |
| European (non-Finnish) | 20.6% | 5 |
| Remaining individualsnot grpmax-eligible | 19.5% | 5 |
| East Asian | 18.4% | 5 |
| Admixed American | 11.4% | 9 |
| African / African-American | 4.05% | 25 |
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
- CHRNA7
- Protein
- p.Asn445=
- Coding
- c.1335C>T
- MANE Select
- NM_000746
- dbSNP
- rs2253967
- Type
- single nucleotide variant
- Location
- chr15:32168284 (GRCh38)
- Gene constraint
- LOEUF 1.064 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.16 · 51 PDB
- Residue 445
- an α-helix
Similar variants
- CHRNA7 p.Asn381Asp Uncertain significance ★★ ⚠ same type
- CHRNA7 p.Val374Met Uncertain significance ★★ ⚠ same type
- CHRNA7 c.196-4G>T Likely benign ★★ same type
- CHRNA7 c.240+113C>A Benign ★★ same type
- CHRNA7 c.350+304G>A Likely benign ★★ same type
- CHRNA7 c.55+77G>A Benign ★★ same type
- CHRNA7 c.598+86C>T Benign ★★ same type
- CHRNA7 c.599-111T>A Benign ★★ same type
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/chrna7-p-asn445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown