NPHS2 p.Arg50=
c.148C>A · rs886045596 · VCV1144653
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00272%, 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 2.7 | GERP 0.077, phastCons 0.12 |
| Overall | ||
| CADD | 5.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00272%
African / African-American · 2/73,640 alleles
Filtering AF
0.000451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000169%
Overall
0.000129%
2/1,553,240 alleles · very rare
exomes 0/1,401,134 · genomes 2/152,106 · 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
- NPHS2
- Protein
- p.Arg50=
- Coding
- c.148C>A
- MANE Select
- NM_014625
- dbSNP
- rs886045596
- Type
- single nucleotide variant
- Location
- chr1:179575717 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.00
- Residue 50
- a UniProt-annotated variant site (in nphs2); the 'disordered' region
Similar variants
- NPHS2 p.Arg50Trp Uncertain significance ★★ ⚠ same residue
- NPHS2 c.275-2A>G Pathogenic/Likely pathogenic ★★ same type
- NPHS2 c.378+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHS2 c.451+2T>A Likely pathogenic ★★ same type
- NPHS2 c.451+3A>T Pathogenic/Likely pathogenic ★★ same type
- NPHS2 c.535-1G>T Pathogenic/Likely pathogenic ★★ same type
- NPHS2 c.738+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHS2 c.738+1G>C 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/nphs2-p-arg50 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown