Is NPHP4 p.Val787del (c.2358_2360del) pathogenic?

NPHP4 p.Val787del (c.23582360del) is classified Uncertain significance in NPHP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-28). Ultra-rare (popmax 0.0267%, afr); Associated with nephronophthisis.

What condition is associated with NPHP4 p.Val787del (c.2358_2360del)?

NPHP4 p.Val787del (c.2358_2360del) is associated with nephronophthisis, nephronophthisis 4, Senior-Loken syndrome 4 (ClinVar).

How common is NPHP4 p.Val787del (c.2358_2360del) in the general population?

NPHP4 p.Val787del (c.2358_2360del) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP4 p.Val787del

c.2358_2360del · rs751681273 · VCV1038921

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

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 2.2	GERP 2, phastCons 1
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,948 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,613,334 alleles · ultra-rare exomes 11/1,461,086 · genomes 10/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,747
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: NPHP4
Protein: p.Val787del
Coding: c.2358_2360del
MANE Select: NM_015102
dbSNP: rs751681273
Type: Deletion
Location: chr1:5887411 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

Full NPHP4 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: nephronophthisis 4 Senior-Loken syndrome 4

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP4 p.Val787Met Uncertain significance ★★ ⚠ same residue
NPHP4 c.3817-12_3818del Likely pathogenic ★★ same condition
NPHP4 p.Ala279fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Ala565fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gln1050fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gly1028fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gly529fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Lys424fs Pathogenic/Likely pathogenic ★★ 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/nphp4-p-val787del (accessed [today's date]).

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