Is NPHP3 p.Gly935= (c.2805C>T) pathogenic?

NPHP3 p.Gly935= (c.2805C>T) is classified Pathogenic/Likely pathogenic in NPHP3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-31). Very rare (popmax 0.00439%, sas); Associated with NPHP3-related disorder.

What condition is associated with NPHP3 p.Gly935= (c.2805C>T)?

NPHP3 p.Gly935= (c.2805C>T) is associated with NPHP3-related disorder, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 p.Gly935= (c.2805C>T) in the general population?

NPHP3 p.Gly935= (c.2805C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

NPHP3 p.Gly935=

c.2805C>T · rs1281725083 · VCV996537

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

NPHP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.69	donor gain · deltas
Pangolin	Δ0.48	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.46	GERP -0.87, phastCons 0.003
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

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 0.000558% 9/1,614,076 alleles · very rare exomes 9/1,461,846 · genomes 0/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,771
Admixed American	0.00167%	60,012
African / African-American	0.00133%	75,016
European (non-Finnish)	0.000254%	393,329

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.Gly935=
Coding: c.2805C>T
MANE Select: NM_153240
dbSNP: rs1281725083
Type: single nucleotide variant
Location: chr3:132689152 (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

Also linked: renal-hepatic-pancreatic dysplasia 1 NPHP3-related Meckel-like syndrome nephronophthisis 3 nephronophthisis

Similar variants

NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP3 c.3201+1G>T Likely pathogenic ★★ same condition
NPHP3 c.393+1G>C Likely pathogenic ★★ same condition
NPHP3 c.520-1G>T Pathogenic ★★ same condition
NPHP3 c.823+1G>T Likely pathogenic ★★ same condition
NPHP3 c.958-2A>G Pathogenic ★★ same condition
NPHP3 p.Arg1125Ter Pathogenic ★★ same condition
NPHP3 p.Arg1259Ter 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/nphp3-p-gly935 (accessed [today's date]).

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