Is CEP164 p.Phe1432fs (c.4293_4294del) pathogenic?

CEP164 p.Phe1432fs (c.42934294del) is classified Conflicting classifications of pathogenicity in CEP164 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-06-30). Very rare (popmax 0.005%, amr); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Phe1432fs (c.4293_4294del)?

CEP164 p.Phe1432fs (c.4293_4294del) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Phe1432fs (c.4293_4294del) in the general population?

CEP164 p.Phe1432fs (c.4293_4294del) is very rare (popmax 0.005%, amr) (gnomAD).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Phe1432fs

c.4293_4294del · rs756288878 · VCV1179082

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

nephronophthisis 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (33 of 33) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.25	GERP 0.14
Overall
CADD	22.4	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 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,006 alleles · very rare

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: CEP164
Protein: p.Phe1432fs
Coding: c.4293_4294del
MANE Select: NM_014956
dbSNP: rs756288878
Type: Microsatellite
Location: chr11:117412074 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CEP164 p.Glu265del Uncertain significance ★★ same condition
CEP164 p.Glu659del Uncertain significance ★★ same condition
CEP164 p.Lys267del Uncertain significance ★★ same condition
CEP164 c.3216+20_3216+33del Benign/Likely benign ★★ same condition
CEP164 p.Ser1104fs Pathogenic ★ same condition
CEP164 p.Trp1201fs Pathogenic ★ same condition
CEP164 p.Val902fs Pathogenic ★ same condition
CEP164 p.1310PT[3] 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/cep164-p-phe1432fs (accessed [today's date]).

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