Is NPHP4 p.Arg934= (c.2802C>T) pathogenic?

NPHP4 p.Arg934= (c.2802C>T) is classified Benign in NPHP4 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Common (popmax 74.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Senior-Loken syndrome 4.

What condition is associated with NPHP4 p.Arg934= (c.2802C>T)?

NPHP4 p.Arg934= (c.2802C>T) 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.Arg934=

Q: How common is NPHP4 p.Arg934= (c.2802C>T) in the general population?

NPHP4 p.Arg934= (c.2802C>T) is common (popmax 74.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2802C>T · rs3747992 · VCV95679

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 74.7%, eas) — 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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Overall
CADD	3.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74.7% East Asian · 32,647/43,708 alleles

Filtering AF 74% ClinGen BA1/BS1 input FAF95, joint · FAF99 73.7%

Overall 40% 629,577/1,575,438 alleles · common exomes 572,042/1,423,322 · genomes 57,535/152,116 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	74.7%	1
Admixed American	48.8%	2
South Asian	41.6%	2
Remaining individualsnot grpmax-eligible	40.2%	2
Finnishnot grpmax-eligible	39%	3
European (non-Finnish)	39%	3
Ashkenazi Jewishnot grpmax-eligible	37.4%	3
Middle Eastern	34.4%	3
Amishnot grpmax-eligible	31.7%	3
African / African-American	27.9%	4

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.Arg934=
Coding: c.2802C>T
MANE Select: NM_015102
dbSNP: rs3747992
Type: single nucleotide variant
Location: chr1:5877108 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 934: the 'sufficient for basal bodies localization' region; the 'disordered' 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.Arg934Cys 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-arg934 (accessed [today's date]).

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