Is NPHP4 p.Glu1190= (c.3570A>G) pathogenic?

NPHP4 p.Glu1190= (c.3570A>G) is classified Benign in NPHP4 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 43.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Senior-Loken syndrome 4.

What condition is associated with NPHP4 p.Glu1190= (c.3570A>G)?

NPHP4 p.Glu1190= (c.3570A>G) is associated with Senior-Loken syndrome 4, nephronophthisis 4, nephronophthisis (ClinVar).

How is Senior-Loken syndrome inherited?

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

NPHP4 p.Glu1190=

Q: How common is NPHP4 p.Glu1190= (c.3570A>G) in the general population?

NPHP4 p.Glu1190= (c.3570A>G) is common (popmax 43.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3570A>G · rs555164 · VCV95683

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 43.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Senior-Loken syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -2.9, phastCons 0.97
Overall
CADD	1.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.1% South Asian · 37,994/88,178 alleles

Filtering AF 42.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.6%

Overall 40.3% 639,624/1,588,154 alleles · common exomes 585,860/1,436,130 · genomes 53,764/152,024 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	54.9%	2
Ashkenazi Jewishnot grpmax-eligible	46.1%	2
South Asiangrpmax	43.1%	2
Finnishnot grpmax-eligible	42.6%	2
European (non-Finnish)	41.7%	2
Remaining individualsnot grpmax-eligible	40.1%	2
Middle Eastern	40.1%	2
Admixed American	36.9%	3
East Asian	26.7%	4
African / African-American	20.5%	5

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu1190=
Coding: c.3570A>G
MANE Select: NM_015102
dbSNP: rs555164
Type: single nucleotide variant
Location: chr1:5866447 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 1190: the 'sufficient for basal bodies localization' region

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Senior-Loken syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 4 nephronophthisis

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

NPHP4 p.Glu1190Asp Uncertain significance ★ same residue
NPHP4 c.2304+1G>A Pathogenic ★★ same condition
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.2611+1G>C Pathogenic ★★ same condition
NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.517+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.518-2A>G 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-glu1190 (accessed [today's date]).

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