Is NPHP3 c.1118+16del pathogenic?

NPHP3 c.1118+16del is classified Benign in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Ultra-rare (popmax 0.0132%, afr); Associated with nephronophthisis.

What condition is associated with NPHP3 c.1118+16del?

NPHP3 c.1118+16del is associated with nephronophthisis (ClinVar).

How common is NPHP3 c.1118+16del in the general population?

NPHP3 c.1118+16del is ultra-rare (popmax 0.0132%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 c.1118+16del

rs560151715 · VCV1164848

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, afr)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP -2.4, phastCons 0.68
Non-coding constraint	Z 0.38	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	0.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% African / African-American · 9/67,936 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00958%

Overall 0.0103% 137/1,325,876 alleles · ultra-rare exomes 124/1,173,890 · genomes 13/151,986 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0132%	7,548
European (non-Finnish)	0.0121%	8,298
South Asian	0.00792%	12,626
Remaining individualsnot grpmax-eligible	0.00773%	12,935
East Asian	0.00474%	21,116
Ashkenazi Jewishnot grpmax-eligible	0.00382%	26,206
Admixed American	0.00206%	48,496

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.1118+16del
MANE Select: NM_153240
dbSNP: rs560151715
Type: Deletion
Location: chr3:132713110 (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.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
NPHP3 c.1118+17del 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-c-1118-plus-16del (accessed [today's date]).

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