Is NPHP3 p.Asn347fs (c.1040dup) pathogenic?

NPHP3 p.Asn347fs (c.1040dup) is classified Pathogenic in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). No gnomAD frequency available for this variant; Associated with nephronophthisis.

What condition is associated with NPHP3 p.Asn347fs (c.1040dup)?

NPHP3 p.Asn347fs (c.1040dup) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Asn347fs (c.1040dup) in the general population?

NPHP3 p.Asn347fs (c.1040dup) 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.

NPHP3 p.Asn347fs

c.1040dup · rs2107996325 · VCV1458848

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

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 6 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.3	GERP -1.8, 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: NPHP3
Protein: p.Asn347fs
Coding: c.1040dup
MANE Select: NM_153240
dbSNP: rs2107996325
Type: Duplication
Location: chr3:132713203 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.59 · 1 PDB

Full NPHP3 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

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP3 p.Gln986fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Ser1053fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Ser1271Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Gln1150dup Uncertain significance ★★ same condition
NPHP3 p.Met1fs Uncertain significance ★★ same condition
NPHP3 c.1525-13dup Benign/Likely benign ★★ same condition
NPHP3 c.3125+7dup Benign/Likely benign ★★ same condition
NPHP3 c.3571-10dup Likely benign ★★ 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/nphp3-p-asn347fs (accessed [today's date]).

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