Is NPHP3 c.1887+17del pathogenic?

NPHP3 c.1887+17del is classified Likely benign in NPHP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0214%, afr); Associated with nephronophthisis.

What condition is associated with NPHP3 c.1887+17del?

NPHP3 c.1887+17del is associated with nephronophthisis, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 c.1887+17del in the general population?

NPHP3 c.1887+17del is ultra-rare (popmax 0.0214%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 c.1887+17del

rs772091214 · VCV1533891

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.08	GERP -0.91
Non-coding constraint	Z 0.02	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	1.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,922 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000992% 16/1,613,454 alleles · ultra-rare exomes 7/1,461,196 · genomes 9/152,258 · 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
Coding: c.1887+17del
MANE Select: NM_153240
dbSNP: rs772091214
Type: Deletion
Location: chr3:132699901 (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 c.3570+1del Likely pathogenic ★★ same condition
NPHP3 p.Arg157fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Glu90_Tyr91insTer Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.His559fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Phe1001fs Pathogenic ★★ same condition
NPHP3 p.Thr136fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Val363fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 c.3697-11_3697-7del 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-c-1887-plus-17del (accessed [today's date]).

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