NPR2 p.Ser859=
c.2577T>C · rs1422137094 · VCV2939022
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 | 0.236 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.71 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 7.438 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,924 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000186%
3/1,612,544 alleles · very rare
exomes 2/1,460,970 · genomes 1/151,574 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,962 |
| European (non-Finnish) | 8.48e-05% | 1,179,134 |
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.Ser859=
- Coding
- c.2577T>C
- MANE Select
- NM_003995
- dbSNP
- rs1422137094
- Type
- single nucleotide variant
- Location
- chr9:35807080 (GRCh38)
- Gene constraint
- LOEUF 0.517 · pLI 0.45 (gnomAD)
- Structure
- AlphaFold pLDDT 84.00
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-ser859 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown