NPR2 p.Phe779=
c.2337T>C · rs115369552 · VCV366790
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0557%, eas)
Conditions
2
acromesomelic dysplasia 1, Maroteaux type
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.151 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.62 | GERP -1.5, phastCons 0.051 |
| Overall | ||
| CADD | 6.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0557%
East Asian · 25/44,880 alleles
Filtering AF
0.0387%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.033%
Overall
0.00167%
27/1,614,208 alleles · ultra-rare
exomes 24/1,461,894 · genomes 3/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0557% | 1,795 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
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
- NPR2
- Protein
- p.Phe779=
- Coding
- c.2337T>C
- MANE Select
- NM_003995
- dbSNP
- rs115369552
- Type
- single nucleotide variant
- Location
- chr9:35806198 (GRCh38)
- Gene constraint
- LOEUF 0.517 · pLI 0.45 (gnomAD)
- Structure
- AlphaFold pLDDT 84.00
- Residue 779
- the protein kinase domain
Similar variants
- NPR2 c.1887+2T>A Pathogenic/Likely pathogenic ★★ same condition
- NPR2 p.Arg299Ter Pathogenic ★★ same condition
- NPR2 p.Arg363Ter Pathogenic ★★ same condition
- NPR2 p.Arg388Gln Pathogenic ★★ same condition
- NPR2 p.Arg479Ter Pathogenic/Likely pathogenic ★★ same condition
- NPR2 p.Arg741Ter Pathogenic/Likely pathogenic ★★ same condition
- NPR2 p.Arg749Trp Pathogenic/Likely pathogenic ★★ same condition
- NPR2 p.Arg767Ter Pathogenic ★★ same condition
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/npr2-p-phe779 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown