Is NPHP4 p.Arg871Ter (c.2611C>T) pathogenic?

NPHP4 p.Arg871Ter (c.2611C>T) is classified Pathogenic/Likely pathogenic in NPHP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-24). Very rare (popmax 0.000593%, nfe); Associated with NPHP4-related disorder.

What condition is associated with NPHP4 p.Arg871Ter (c.2611C>T)?

NPHP4 p.Arg871Ter (c.2611C>T) is associated with NPHP4-related disorder, nephronophthisis (ClinVar).

How common is NPHP4 p.Arg871Ter (c.2611C>T) in the general population?

NPHP4 p.Arg871Ter (c.2611C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

NPHP4 p.Arg871Ter

c.2611C>T · rs2100733826 · VCV1455063

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 0.000593%, nfe)

Conditions

NPHP4-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 19 of 30
Splicing
SpliceAI	Δ0.92	donor gain · deltas
Pangolin	Δ0.69	gain · loss 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1	GERP -3.4
Overall
CADD	38.0	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 0.000593% European (non-Finnish) · 7/1,179,710 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,584 alleles · very rare exomes 7/1,461,346 · genomes 0/152,238 · 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: NPHP4
Protein: p.Arg871Ter
Coding: c.2611C>T
MANE Select: NM_015102
dbSNP: rs2100733826
Type: single nucleotide variant
Location: chr1:5880114 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 871: the 'sufficient for basal bodies localization' region

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: nephronophthisis

Similar variants

NPHP4 c.2304+1G>A Pathogenic ★★ same condition
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.2611+1G>C Pathogenic ★★ same condition
NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.517+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.518-2A>G Likely pathogenic ★★ same condition
NPHP4 c.992+2T>C 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/nphp4-p-arg871ter (accessed [today's date]).

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