Is NPHP3 p.Ser80= (c.240G>C) pathogenic?

NPHP3 p.Ser80= (c.240G>C) is classified Likely benign in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). Ultra-rare (popmax 0.0176%, sas); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ser80= (c.240G>C)?

NPHP3 p.Ser80= (c.240G>C) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Ser80= (c.240G>C) in the general population?

NPHP3 p.Ser80= (c.240G>C) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP3 p.Ser80=

c.240G>C · rs1940247250 · VCV2061932

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Conditions

nephronophthisis

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.20	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -3.8	GERP -0.36
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,012 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.000997% 16/1,604,802 alleles · ultra-rare exomes 14/1,452,628 · genomes 2/152,174 · 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.Ser80=
Coding: c.240G>C
MANE Select: NM_153240
dbSNP: rs1940247250
Type: single nucleotide variant
Location: chr3:132722116 (GRCh38)

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)

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-ser80 (accessed [today's date]).

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