NPHS2 p.Ser48=
c.144C>G · rs111306764 · VCV1930736
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00473%, sas)
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 -1.5 | GERP -2.4 |
| Overall | ||
| CADD | 0.551 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00473%
South Asian · 4/84,554 alleles
Filtering AF
0.0016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000944%
Overall
0.000259%
4/1,543,834 alleles · very rare
exomes 4/1,391,658 · genomes 0/152,176 · 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.Ser48=
- Coding
- c.144C>G
- MANE Select
- NM_014625
- dbSNP
- rs111306764
- Type
- single nucleotide variant
- Location
- chr1:179575721 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.00
- Residue 48
- a UniProt-annotated variant site (in nphs2); the 'disordered' region
Similar variants
- NPHS2 p.Ser48Tyr Uncertain significance ★ ⚠ same residue
- NPHS2 p.Ser48fs 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
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-ser48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown