Is NPHP3 p.Glu1292del (c.3872AAG[1]) pathogenic?

NPHP3 p.Glu1292del (c.3872AAG[1]) is classified Uncertain significance in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Very rare (popmax 0.00017%, nfe); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Glu1292del (c.3872AAG[1])?

NPHP3 p.Glu1292del (c.3872AAG[1]) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Glu1292del (c.3872AAG[1]) in the general population?

NPHP3 p.Glu1292del (c.3872AAG[1]) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 p.Glu1292del

c.3872AAG[1] · rs1200012206 · VCV949854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,834 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,890 alleles · very rare exomes 2/1,461,680 · genomes 0/152,210 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NPHP3
Protein: p.Glu1292del
Coding: c.3872AAG[1]
MANE Select: NM_153240
dbSNP: rs1200012206
Type: Microsatellite
Location: chr3:132682026 (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.Glu1292Ala Uncertain significance ★★ ⚠ same residue
NPHP3 p.Ala1135fs Pathogenic ★★ same condition
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

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-glu1292del (accessed [today's date]).

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