NPHS2 p.Ser205=
c.615C>T · rs778514784 · VCV749073
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.035%, amr)
Conditions
1
steroid-resistant nephrotic syndrome
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 0.29 | GERP -2.4, phastCons 0.32 |
| Overall | ||
| CADD | 6.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.035%
Admixed American · 21/59,984 alleles
Filtering AF
0.0234%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.0013%
21/1,613,888 alleles · ultra-rare
exomes 19/1,461,730 · genomes 2/152,158 · 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.Ser205=
- Coding
- c.615C>T
- MANE Select
- NM_014625
- dbSNP
- rs778514784
- Type
- single nucleotide variant
- Location
- chr1:179557150 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.00
- Residue 205
- a UniProt-annotated variant site (in nphs2)
Similar variants
- NPHS2 c.535-1G>T Pathogenic/Likely pathogenic ★★ same condition
- NPHS2 c.738+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHS2 c.738+1G>C Pathogenic ★★ same condition
- NPHS2 p.Arg138Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NPHS2 p.Arg138Ter Pathogenic ★★ same condition
- NPHS2 p.Arg168Cys Pathogenic/Likely pathogenic ★★ same condition
- NPHS2 p.Arg168His Pathogenic/Likely pathogenic ★★ same condition
- NPHS2 p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
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-ser205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown