Is NPHP4 p.Ser251fs (c.750dup) pathogenic?

NPHP4 p.Ser251fs (c.750dup) is classified Pathogenic in NPHP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-04). No gnomAD frequency available for this variant; Associated with nephronophthisis.

What condition is associated with NPHP4 p.Ser251fs (c.750dup)?

NPHP4 p.Ser251fs (c.750dup) is associated with nephronophthisis, nephronophthisis 4 (ClinVar).

How common is NPHP4 p.Ser251fs (c.750dup) in the general population?

NPHP4 p.Ser251fs (c.750dup) is no gnomAD frequency available for this variant (gnomAD).

How is Nephronophthisis inherited?

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

NPHP4 p.Ser251fs

c.750dup · rs754862360 · VCV829848

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nephronophthisis

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 7 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 0.75, 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: NPHP4
Protein: p.Ser251fs
Coding: c.750dup
MANE Select: NM_015102
dbSNP: rs754862360
Type: Duplication
Location: chr1:5952759 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 4

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

NPHP4 p.Ser251= Likely benign ★ same residue
NPHP4 p.His982fs Pathogenic ★★ same condition
NPHP4 p.Leu970fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Ser1092fs Pathogenic ★★ same condition
NPHP4 p.Thr1004fs Pathogenic ★★ same condition
NPHP4 c.1306_1314dup Uncertain significance ★★ same condition
NPHP4 c.3231+7dup Likely benign ★★ same condition
NPHP4 p.Ala1029fs 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/nphp4-p-ser251fs (accessed [today's date]).

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