NPR1 p.Pro453=
c.1359C>T · rs148618212 · VCV2639349
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.858%, mid)
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 -0.32 | GERP -2.4, phastCons 0.001 |
| Overall | ||
| CADD | 9.625 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.858%
Middle Eastern · 52/6,062 alleles
Filtering AF
0.672%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.605%
Overall
0.0994%
1,604/1,614,186 alleles · rare
exomes 1,461/1,461,888 · genomes 143/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.858% | 117 |
| Admixed American | 0.237% | 423 |
| Remaining individualsnot grpmax-eligible | 0.117% | 856 |
| European (non-Finnish) | 0.106% | 946 |
| South Asian | 0.0538% | 1,859 |
| Finnishnot grpmax-eligible | 0.0328% | 3,049 |
| African / African-American | 0.0253% | 3,950 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
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
- NPR1
- Protein
- p.Pro453=
- Coding
- c.1359C>T
- MANE Select
- NM_000906
- dbSNP
- rs148618212
- Type
- single nucleotide variant
- Location
- chr1:153683471 (GRCh38)
- Gene constraint
- LOEUF 0.671 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.82 · 14 PDB
Similar variants
- NPR1 c.1605+9G>A Likely benign ★★ same type
- NPR1 p.Glu967Lys Benign ★★ ⚠ same type
- NPR1 p.Gly618= Benign ★★ same type
- NPR1 c.2757+1G>A Uncertain significance ★ same type
- NPR1 p.Ala139Thr Uncertain significance ★ same type
- NPR1 p.Ala170Val Uncertain significance ★ ⚠ same type
- NPR1 p.Ala258Gly Uncertain significance ★ ⚠ same type
- NPR1 p.Ala261Thr Uncertain significance ★ ⚠ 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/npr1-p-pro453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown