Is NEK8 p.Phe384= (c.1152C>T) pathogenic?

NEK8 p.Phe384= (c.1152C>T) is classified Likely benign in NEK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Absent from gnomAD v4.1; Associated with nephronophthisis 9.

What condition is associated with NEK8 p.Phe384= (c.1152C>T)?

NEK8 p.Phe384= (c.1152C>T) is associated with nephronophthisis 9 (ClinVar).

How common is NEK8 p.Phe384= (c.1152C>T) in the general population?

NEK8 p.Phe384= (c.1152C>T) is absent from gnomAD v4.1 (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NEK8 p.Phe384=

c.1152C>T · VCV4798926

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

nephronophthisis 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.039	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.6, phastCons 1
Overall
CADD	13.2	PHRED · no single calibrated threshold — expert panels disagree

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: NEK8
Protein: p.Phe384=
Coding: c.1152C>T
MANE Select: NM_178170
Type: single nucleotide variant
Location: chr17:28738175 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.23
Residue 384: a UniProt-annotated variant site (in rhpd2; likely pathogenic; loss of protein expression)

Full NEK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

NEK8 c.1418-1G>A Pathogenic/Likely pathogenic ★★ same condition
NEK8 c.828-1G>C Pathogenic/Likely pathogenic ★★ same condition
NEK8 c.889+1G>T Likely pathogenic ★★ same condition
NEK8 p.Arg127Ter Pathogenic/Likely pathogenic ★★ same condition
NEK8 p.Arg499Ter Pathogenic/Likely pathogenic ★★ same condition
NEK8 p.Arg599Ter Pathogenic/Likely pathogenic ★★ same condition
NEK8 p.Glu444Ter Pathogenic/Likely pathogenic ★★ same condition
NEK8 c.2050+1G>A Uncertain significance ★★ 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/nek8-p-phe384 (accessed [today's date]).

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