Is NPHP1 p.Arg530Ter (c.1588C>T) pathogenic?

NPHP1 p.Arg530Ter (c.1588C>T) is classified Pathogenic in NPHP1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-05-22). Very rare (popmax 0.00223%, eas); Associated with nephronophthisis 1.

What condition is associated with NPHP1 p.Arg530Ter (c.1588C>T)?

NPHP1 p.Arg530Ter (c.1588C>T) is associated with nephronophthisis 1, Senior-Loken syndrome 1, Joubert syndrome with renal defect (ClinVar).

How common is NPHP1 p.Arg530Ter (c.1588C>T) in the general population?

NPHP1 p.Arg530Ter (c.1588C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NPHP1 p.Arg530Ter

c.1588C>T · rs547352656 · VCV1030710

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

nephronophthisis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 20
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.6	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,842 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,240 alleles · very rare exomes 21/1,461,058 · genomes 5/152,182 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,842
European (non-Finnish)	0.00204%	49,139
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: NPHP1
Protein: p.Arg530Ter
Coding: c.1588C>T
MANE Select: NM_001128178
dbSNP: rs547352656
Type: single nucleotide variant
Location: chr2:110131733 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Senior-Loken syndrome 1 Joubert syndrome with renal defect nephronophthisis

Similar variants

NPHP1 p.Arg530Gln Uncertain significance ★★ ⚠ same residue
NPHP1 c.1083+1G>A Likely pathogenic ★★ same condition
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.329+1G>A 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/nphp1-p-arg530ter (accessed [today's date]).

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