Is NPHP3 p.Arg142Ter (c.424C>T) pathogenic?

NPHP3 p.Arg142Ter (c.424C>T) is classified Pathogenic/Likely pathogenic in NPHP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-10). Ultra-rare (popmax 0.0113%, eas); Associated with NPHP3-related disorder.

What condition is associated with NPHP3 p.Arg142Ter (c.424C>T)?

NPHP3 p.Arg142Ter (c.424C>T) is associated with NPHP3-related disorder, nephronophthisis 3, nephronophthisis (ClinVar).

How common is NPHP3 p.Arg142Ter (c.424C>T) in the general population?

NPHP3 p.Arg142Ter (c.424C>T) is ultra-rare (popmax 0.0113%, eas) (gnomAD).

NPHP3 p.Arg142Ter

c.424C>T · rs771742823 · VCV430726

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, eas)

Conditions

NPHP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 27
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Pangolin	Δ0.39	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0113% East Asian · 5/44,344 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.000438% 7/1,596,410 alleles · ultra-rare exomes 5/1,444,962 · genomes 2/151,448 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0113%	8,869
European (non-Finnish)	0.000171%	584,727

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.Arg142Ter
Coding: c.424C>T
MANE Select: NM_153240
dbSNP: rs771742823
Type: single nucleotide variant
Location: chr3:132719800 (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: 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-arg142ter (accessed [today's date]).

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