Is NPHP3 p.Ser611fs (c.1832_1833del) pathogenic?

NPHP3 p.Ser611fs (c.18321833del) is classified Pathogenic in NPHP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-06). Very rare (popmax 0.00439%, sas); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ser611fs (c.1832_1833del)?

NPHP3 p.Ser611fs (c.1832_1833del) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Ser611fs (c.1832_1833del) in the general population?

NPHP3 p.Ser611fs (c.1832_1833del) is very rare (popmax 0.00439%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 p.Ser611fs

c.1832_1833del · rs780165789 · VCV1454798

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

nephronophthisis

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 12 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,614,078 alleles · very rare exomes 8/1,461,850 · genomes 0/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,771
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000169%	590,005

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.Ser611fs
Coding: c.1832_1833del
MANE Select: NM_153240
dbSNP: rs780165789
Type: Microsatellite
Location: chr3:132699972 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.59 · 1 PDB

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)

Similar variants

NPHP3 p.Ala1135fs Pathogenic ★★ same condition
NPHP3 p.Glu145fs Pathogenic ★★ same condition
NPHP3 p.Gly1275del Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Leu365fs Pathogenic ★★ same condition
NPHP3 p.Ser960fs Pathogenic ★ same condition
NPHP3 c.3813-12TC[2] Uncertain significance ★ same condition
NPHP3 p.Glu1292del Uncertain significance ★ same condition
NPHP3 p.Leu110del Conflicting classifications of pathogenicity ★ 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/nphp3-p-ser611fs (accessed [today's date]).

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