NPHS2 p.Phe176=
c.528T>C · rs1674062813 · VCV1137113
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -0.78, phastCons 1 |
| Overall | ||
| CADD | 8.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,040 alleles
Filtering AF
0.000126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.2e-05%
Overall
0.000379%
6/1,583,106 alleles · ultra-rare
exomes 5/1,430,928 · genomes 1/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,040 |
| European (non-Finnish) | 0.000431% | 232,160 |
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.Phe176=
- Coding
- c.528T>C
- MANE Select
- NM_014625
- dbSNP
- rs1674062813
- Type
- single nucleotide variant
- Location
- chr1:179559685 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.00
- Residue 176
- a UniProt-annotated variant site (in nphs2)
Similar variants
- NPHS2 p.Phe176fs Likely pathogenic ★ 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-phe176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown