NPRL2 p.Pro167=
c.501G>A · rs35968178 · VCV707379
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.08%, afr)
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 -1.1 | GERP -4.9 |
| Overall | ||
| CADD | 6.386 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.08%
African / African-American · 813/75,016 alleles
Filtering AF
1.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.997%
Overall
0.0604%
975/1,614,058 alleles · low-frequency
exomes 494/1,461,774 · genomes 481/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.08% | 92 |
| Admixed American | 0.13% | 770 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,157 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.00439% | 22,770 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.00203% | 49,168 |
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
- NPRL2
- Protein
- p.Pro167=
- Coding
- c.501G>A
- MANE Select
- NM_006545
- dbSNP
- rs35968178
- Type
- single nucleotide variant
- Location
- chr3:50348958 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.58 (gnomAD)
- Structure
- AlphaFold pLDDT 69.38 · 10 PDB
- Residue 167
- an α-helix
Similar variants
- NPRL2 p.Pro167Leu Uncertain significance ★ ⚠ same residue
- NPR2 c.1436+1G>T Likely pathogenic ★★ same type
- NPR2 c.1887+2T>A Pathogenic/Likely pathogenic ★★ same type
- NPR2 p.Arg299Ter Pathogenic ★★ same type
- NPR2 p.Arg363Ter Pathogenic ★★ same type
- NPR2 p.Arg388Gln Pathogenic ★★ same type
- NPR2 p.Arg479Ter Pathogenic/Likely pathogenic ★★ same type
- NPR2 p.Arg741Ter Pathogenic/Likely pathogenic ★★ 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/nprl2-p-pro167 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown