NOS2 p.Cys635=
c.1905C>T · rs202098132 · VCV3046531
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
1
NOS2-related disorder
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 -5.8 | GERP -1.5 |
| Overall | ||
| CADD | 7.337 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.011%
177/1,612,674 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0406% | 2,464 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| East Asian | 0.0312% | 3,205 |
| Admixed American | 0.025% | 3,995 |
| European (non-Finnish) | 0.0089% | 11,236 |
| African / African-American | 0.00799% | 12,508 |
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
- NOS2
- Protein
- p.Cys635=
- Coding
- c.1905C>T
- MANE Select
- NM_001029861 · reported on NM_000625
- dbSNP
- rs202098132
- Type
- single nucleotide variant
- Location
- chr17:27769106 (GRCh38)
- Structure
- AlphaFold pLDDT 76.58
Disease context
NOS2-related disorder
Similar variants
- NOS2 p.Gln1097= Likely benign same condition
- NOS2 p.Thr182Met Likely benign ⚠ same condition
- NOS2 p.Thr245= Likely benign same condition
- NOS2 c.1005-10T>C Benign ★★ same type
- NOS2 p.Arg1018Ser Likely benign ★★ same type
- NOS2 p.Glu1111= Benign/Likely benign ★★ same type
- NOS2 p.Gly360= Likely benign ★★ same type
- NOS2 p.Phe319= 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/nos2-p-cys635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown