Is NPHP4 p.Ser1067Arg (c.3201C>G) pathogenic?

NPHP4 p.Ser1067Arg (c.3201C>G) is classified Uncertain significance in NPHP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-20). AlphaMissense: likely pathogenic (0.6514); Absent from gnomAD v4.1; Associated with NPHP4-related disorder.

What condition is associated with NPHP4 p.Ser1067Arg (c.3201C>G)?

NPHP4 p.Ser1067Arg (c.3201C>G) is associated with NPHP4-related disorder (ClinVar).

How common is NPHP4 p.Ser1067Arg (c.3201C>G) in the general population?

NPHP4 p.Ser1067Arg (c.3201C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NPHP4 p.Ser1067Arg (c.3201C>G)?

AlphaMissense predicts likely pathogenic (score 0.6514) — an in-silico prediction, not a clinical call.

NPHP4 p.Ser1067Arg

c.3201C>G · rs2523114980 · VCV3061351

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

NPHP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.6514	likely pathogenic
REVEL	0.399	indeterminate
SaProt	LLR -6.29	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 123 kb · p 0.49 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NPHP4
Protein: p.Ser1067Arg
Coding: c.3201C>G
MANE Select: NM_015102
dbSNP: rs2523114980
Type: single nucleotide variant
Location: chr1:5874501 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 1067: the 'sufficient for basal bodies localization' region

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

Disease context

NPHP4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP4 p.Ser1067Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.517+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Arg59Ter Pathogenic ★★ same condition
NPHP4 p.Arg871Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gln646Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gln671Ter 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/nphp4-p-ser1067arg (accessed [today's date]).

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