Is NPHS2 p.Pro43fs (c.104_126dup) pathogenic?

NPHS2 p.Pro43fs (c.104126dup) is classified Pathogenic in NPHS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). No gnomAD frequency available for this variant; Associated with nephrotic syndrome, type 2.

What condition is associated with NPHS2 p.Pro43fs (c.104_126dup)?

NPHS2 p.Pro43fs (c.104_126dup) is associated with nephrotic syndrome, type 2 (ClinVar).

How common is NPHS2 p.Pro43fs (c.104_126dup) in the general population?

NPHS2 p.Pro43fs (c.104_126dup) is no gnomAD frequency available for this variant (gnomAD).

NPHS2 p.Pro43fs

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.104_126dup · rs2526379067 · VCV3239972

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nephrotic syndrome, type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -2, phastCons 0.05

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.Pro43fs
Coding: c.104_126dup
MANE Select: NM_014625
dbSNP: rs2526379067
Type: Duplication
Location: chr1:179575738 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.00
Residue 43: a UniProt-annotated variant site (in nphs2); the 'disordered' region

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

Similar variants

NPHS2 p.Arg36fs Pathogenic ★★ same condition
NPHS2 p.Ser46fs Likely pathogenic ★★ same condition
NPHS2 p.Ser48fs Likely pathogenic ★★ same condition
NPHS2 c.451+9dup Benign/Likely benign ★★ same condition
NPHS2 p.Ala61fs Likely pathogenic ★ same condition
NPHS2 p.Asn199fs Pathogenic ★ same condition
NPHS2 p.Lys22fs Likely pathogenic ★ same condition
NPHS2 p.Pro157fs 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-pro43fs (accessed [today's date]).

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