Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.86%, sas)
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 -5.2 | GERP -4.3 |
| Overall | ||
| CADD | 1.902 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.86%
South Asian · 2,606/91,028 alleles
Filtering AF
2.77%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.73%
Overall
0.45%
7,246/1,611,692 alleles · low-frequency
exomes 6,769/1,459,420 · genomes 477/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.86% | 35 |
| Middle Eastern | 0.958% | 104 |
| Remaining individualsnot grpmax-eligible | 0.566% | 177 |
| European (non-Finnish) | 0.328% | 305 |
| Ashkenazi Jewishnot grpmax-eligible | 0.277% | 361 |
| East Asian | 0.181% | 553 |
| African / African-American | 0.152% | 658 |
| Admixed American | 0.138% | 723 |
| Finnishnot grpmax-eligible | 0.00943% | 10,603 |
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
- NOS1
- Protein
- p.Pro140=
- Coding
- c.420G>A
- MANE Select
- NM_000620
- dbSNP
- rs9658278
- Type
- single nucleotide variant
- Location
- chr12:117330650 (GRCh38)
- Structure
- AlphaFold pLDDT 61.90 · 1 PDB
Similar variants
- NANOS1 c.-51G>C Benign ★★ same type
- NANOS1 p.Pro34Thr Benign ★★ same type
- NOS1 c.3042-6C>T Benign ★★ same type
- NOS1 p.Ala1337= Likely benign ★★ same type
- NOS1 p.Asp241Asn Benign/Likely benign ★★ same type
- NOS1 p.Asp394Ala Benign/Likely benign ★★ same type
- NOS1 p.Gly595Ser Benign/Likely benign ★★ same type
- NOS1 p.Gly864Asp Likely 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/nos1-p-pro140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown