NPHS2 p.Arg58=
c.172C>A · rs780396665 · VCV2847759
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00173%, amr)
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 2.5 | GERP 0.087, phastCons 0.74 |
| Overall | ||
| CADD | 11.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00173%
Admixed American · 1/57,674 alleles
Overall
6.3e-05%
1/1,588,418 alleles · very rare
exomes 1/1,436,222 · genomes 0/152,196 · 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.Arg58=
- Coding
- c.172C>A
- MANE Select
- NM_014625
- dbSNP
- rs780396665
- Type
- single nucleotide variant
- Location
- chr1:179575693 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.00
- Residue 58
- a UniProt-annotated variant site (in nphs2); the 'disordered' region
Similar variants
- 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
- NPHS2 c.738+2T>C 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/nphs2-p-arg58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown