NOS1 p.Glu2=
c.6G>A · rs759679932 · VCV735440
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0635%, amr)
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 1.8 | GERP 0.027, phastCons 1 |
| Overall | ||
| CADD | 9.609 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0635%
Admixed American · 38/59,816 alleles
Filtering AF
0.0475%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.042%
Overall
0.00261%
42/1,608,838 alleles · ultra-rare
exomes 38/1,456,688 · genomes 4/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0635% | 1,574 |
| African / African-American | 0.00267% | 37,419 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,236 |
| South Asian | 0.00111% | 90,458 |
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.Glu2=
- Coding
- c.6G>A
- MANE Select
- NM_000620
- dbSNP
- rs759679932
- Type
- single nucleotide variant
- Location
- chr12:117331064 (GRCh38)
- Structure
- AlphaFold pLDDT 61.90 · 1 PDB
- Residue 2
- the 'disordered' region
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-glu2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown