Is NPHP3 p.Ala1135fs (c.3402_3403del) pathogenic?

NPHP3 p.Ala1135fs (c.34023403del) is classified Pathogenic in NPHP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-12). No gnomAD frequency available for this variant; Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ala1135fs (c.3402_3403del)?

NPHP3 p.Ala1135fs (c.3402_3403del) is associated with nephronophthisis, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 p.Ala1135fs (c.3402_3403del) in the general population?

NPHP3 p.Ala1135fs (c.3402_3403del) 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.Ala1135fs

c.3402_3403del · rs746849675 · VCV1069581

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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 24 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, 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.Ala1135fs
Coding: c.3402_3403del
MANE Select: NM_153240
dbSNP: rs746849675
Type: Microsatellite
Location: chr3:132684721 (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

Also linked: renal-hepatic-pancreatic dysplasia 1 NPHP3-related Meckel-like syndrome nephronophthisis 3

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP3 p.Glu145fs Pathogenic ★★ same condition
NPHP3 p.Gly1275del Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Leu365fs Pathogenic ★★ same condition
NPHP3 p.Ser611fs Pathogenic ★★ same condition
NPHP3 p.Ser960fs Pathogenic ★ same condition
NPHP3 c.3813-12TC[2] Uncertain significance ★ same condition
NPHP3 p.Glu1292del Uncertain significance ★ same condition
NPHP3 p.Leu110del Conflicting classifications of pathogenicity ★ 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-ala1135fs (accessed [today's date]).

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