NOS1AP p.Pro286=
c.858G>A · VCV4920004
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.183%, afr)
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 -8.7 | GERP -5.1 |
| Overall | ||
| CADD | 1.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.183%
African / African-American · 137/75,000 alleles
Filtering AF
0.158%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.148%
Overall
0.00992%
160/1,613,236 alleles · rare
exomes 62/1,461,038 · genomes 98/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.183% | 547 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.005% | 20,000 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| East Asian | 0.00223% | 44,864 |
| South Asian | 0.0022% | 45,537 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- NOS1AP
- Protein
- p.Pro286=
- Coding
- c.858G>A
- MANE Select
- NM_014697
- Type
- single nucleotide variant
- Location
- chr1:162357055 (GRCh38)
- Gene constraint
- LOEUF 0.495 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 65.59
Similar variants
- NOS1AP p.Pro286Arg Uncertain significance ★ ⚠ same residue
- NOS1AP p.Pro286Leu Uncertain significance ★ ⚠ same residue
- NOS1AP p.Lys427Arg Uncertain significance ★★ ⚠ same type
- NOS1AP p.Pro402Leu Uncertain significance ★★ ⚠ same type
- NOS1AP c.1105+65T>C Benign ★★ same type
- NOS1AP c.178-101C>G Benign ★★ same type
- NOS1AP c.270+55A>G Benign ★★ same type
- NOS1AP c.345-118C>T 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/nos1ap-p-pro286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown