Is NPHP3 p.Ser1271Ter (c.3810dup) pathogenic?

NPHP3 p.Ser1271Ter (c.3810dup) is classified Pathogenic/Likely pathogenic in NPHP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-10). Very rare (popmax 0.000172%, nfe); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ser1271Ter (c.3810dup)?

NPHP3 p.Ser1271Ter (c.3810dup) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Ser1271Ter (c.3810dup) in the general population?

NPHP3 p.Ser1271Ter (c.3810dup) is very rare (popmax 0.000172%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 p.Ser1271Ter

c.3810dup · rs2530374916 · VCV2740922

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Conditions

nephronophthisis

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (26 of 27, 1 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,161,018 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,593,010 alleles · very rare exomes 2/1,440,714 · genomes 0/152,296 · 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: NPHP3
Protein: p.Ser1271Ter
Coding: c.3810dup
MANE Select: NM_153240
dbSNP: rs2530374916
Type: Duplication
Location: chr3:132682704 (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.Gln986fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Ser1053fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Gln1150dup Uncertain significance ★★ same condition
NPHP3 p.Met1fs Uncertain significance ★★ same condition
NPHP3 c.1525-13dup Benign/Likely benign ★★ same condition
NPHP3 c.3125+7dup Benign/Likely benign ★★ same condition
NPHP3 c.3571-10dup Likely benign ★★ same condition
NPHP3 p.Asn347fs 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/nphp3-p-ser1271ter (accessed [today's date]).

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