Is NPHP3 p.Ala158fs (c.447_471dup) pathogenic?

NPHP3 p.Ala158fs (c.447471dup) is classified Likely pathogenic in NPHP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-07). No gnomAD frequency available for this variant; Associated with NPHP3-related disorder.

What condition is associated with NPHP3 p.Ala158fs (c.447_471dup)?

NPHP3 p.Ala158fs (c.447_471dup) is associated with NPHP3-related disorder (ClinVar).

How common is NPHP3 p.Ala158fs (c.447_471dup) in the general population?

NPHP3 p.Ala158fs (c.447_471dup) is no gnomAD frequency available for this variant (gnomAD).

NPHP3 p.Ala158fs

c.447_471dup · rs1553775392 · VCV423303

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

NPHP3-related disorder

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 2 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHP3
Protein: p.Ala158fs
Coding: c.447_471dup
MANE Select: NM_153240
dbSNP: rs1553775392
Type: Duplication
Location: chr3:132719752 (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

NPHP3-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP3 p.Ser1053fs Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Leu513fs Likely pathogenic ★ same condition
NPHP3 p.Leu599Ter Likely pathogenic ★ same condition
NPHP3 p.Ala158Val Uncertain significance ★ ⚠ same residue
NPHP3 p.Ala158= Likely benign ★ same residue
NPHP3 c.3126-12dup Likely benign same condition
NPHP3 c.3570+1del Likely pathogenic ★★ same condition
NPHP3 c.823+1G>T 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-ala158fs (accessed [today's date]).

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