NPR2 p.Ala28=
c.84G>C · VCV3747981
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000593%, nfe)
Conditions
2
acromesomelic dysplasia 1, Maroteaux type
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 -0.55 | GERP -3.5, phastCons 0.001 |
| Overall | ||
| CADD | 8.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000593%
European (non-Finnish) · 7/1,179,892 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000435%
7/1,610,494 alleles · very rare
exomes 7/1,458,170 · genomes 0/152,324 · joint denominator
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.Ala28=
- Coding
- c.84G>C
- MANE Select
- NM_003995
- Type
- single nucleotide variant
- Location
- chr9:35792492 (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-ala28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown