NOS1AP p.Val243=
c.729A>G · VCV4919997
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.34 | GERP -5, phastCons 0.002 |
| Overall | ||
| CADD | 2.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00124%
20/1,614,048 alleles · ultra-rare
exomes 19/1,461,888 · genomes 1/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00667% | 14,999 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| South Asian | 0.0022% | 45,541 |
| European (non-Finnish) | 0.000847% | 118,003 |
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.Val243=
- Coding
- c.729A>G
- MANE Select
- NM_014697
- Type
- single nucleotide variant
- Location
- chr1:162355320 (GRCh38)
- Gene constraint
- LOEUF 0.495 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 65.59
- Residue 243
- the 'disordered' region
Similar variants
- 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
- NOS1AP c.345-172T>C Benign ★★ same type
- NOS1AP c.454-107A>G 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-val243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown