Is NPHS2 p.Lys299fs (c.896del) pathogenic?

NPHS2 p.Lys299fs (c.896del) is classified Likely pathogenic in NPHS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-01). No gnomAD frequency available for this variant; Associated with nephrotic syndrome, type 2.

What condition is associated with NPHS2 p.Lys299fs (c.896del)?

NPHS2 p.Lys299fs (c.896del) is associated with nephrotic syndrome, type 2 (ClinVar).

How common is NPHS2 p.Lys299fs (c.896del) in the general population?

NPHS2 p.Lys299fs (c.896del) is no gnomAD frequency available for this variant (gnomAD).

NPHS2 p.Lys299fs

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.896del · rs2526152738 · VCV2677348

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nephrotic syndrome, type 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP 0.18, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHS2
Protein: p.Lys299fs
Coding: c.896del
MANE Select: NM_014625
dbSNP: rs2526152738
Type: Deletion
Location: chr1:179551429 (GRCh38)

Full NPHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

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-lys299fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown