Is NPHP1 p.Arg320fs (c.958del) pathogenic?

NPHP1 p.Arg320fs (c.958del) is classified Likely pathogenic in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). Very rare (popmax 0.00223%, eas); Associated with Joubert syndrome with renal defect.

What condition is associated with NPHP1 p.Arg320fs (c.958del)?

NPHP1 p.Arg320fs (c.958del) is associated with Joubert syndrome with renal defect (ClinVar).

How common is NPHP1 p.Arg320fs (c.958del) in the general population?

NPHP1 p.Arg320fs (c.958del) is very rare (popmax 0.00223%, eas) (gnomAD).

NPHP1 p.Arg320fs

c.958del · rs1482130141 · VCV2677268

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Joubert syndrome with renal defect

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -3.4
Overall
CADD	27.7	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 · 1/44,752 alleles

Overall 6.22e-05% 1/1,607,512 alleles · very rare exomes 0/1,455,554 · genomes 1/151,958 · joint denominator

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.Arg320fs
Coding: c.958del
MANE Select: NM_001128178
dbSNP: rs1482130141
Type: Deletion
Location: chr2:110160252 (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

Joubert syndrome with renal defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP1 c.141_143+40del Likely pathogenic ★★ same condition
NPHP1 p.Asn61fs Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Asp162fs Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Ile517fs Pathogenic ★★ same condition
NPHP1 p.Lys185fs Pathogenic ★★ same condition
NPHP1 p.Lys377fs Pathogenic ★★ same condition
NPHP1 p.Ser129fs Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Ser29fs 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-arg320fs (accessed [today's date]).

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