Is NPHP3 p.Val15= (c.45G>T) pathogenic?

NPHP3 p.Val15= (c.45G>T) is classified Likely benign in NPHP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-27). Very rare (popmax 0.00413%, afr); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Val15= (c.45G>T)?

NPHP3 p.Val15= (c.45G>T) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Val15= (c.45G>T) in the general population?

NPHP3 p.Val15= (c.45G>T) is very rare (popmax 0.00413%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 p.Val15=

c.45G>T · rs768083433 · VCV262715

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00413%, afr)

Conditions

nephronophthisis

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.31	GERP -2, phastCons 0.99
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00413% African / African-American · 3/72,630 alleles

Filtering AF 0.00209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.0024% 38/1,581,830 alleles · very rare exomes 33/1,429,794 · genomes 5/152,036 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00413%	24,210
European (non-Finnish)	0.0029%	34,504
Admixed American	0.00171%	58,430

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.Val15=
Coding: c.45G>T
MANE Select: NM_153240
dbSNP: rs768083433
Type: single nucleotide variant
Location: chr3:132722311 (GRCh38)

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)

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-val15 (accessed [today's date]).

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