Is CEP164 p.Arg897fs (c.2688_2691del) pathogenic?

CEP164 p.Arg897fs (c.26882691del) is classified Pathogenic/Likely pathogenic in CEP164 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-31). Very rare (popmax 0.000254%, nfe); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Arg897fs (c.2688_2691del)?

CEP164 p.Arg897fs (c.2688_2691del) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg897fs (c.2688_2691del) in the general population?

CEP164 p.Arg897fs (c.2688_2691del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Arg897fs

c.2688_2691del · rs1317765862 · VCV1405576

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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	predicted	premature termination codon in exon 21 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -2.4
Overall
CADD	34.0	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 0.000254% European (non-Finnish) · 3/1,179,930 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,714 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.Arg897fs
Coding: c.2688_2691del
MANE Select: NM_014956
dbSNP: rs1317765862
Type: Deletion
Location: chr11:117394419 (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.Arg897Ter Pathogenic/Likely pathogenic ★★ same residue
CEP164 p.Arg897Gln Uncertain significance ★★ ⚠ same residue
CEP164 p.Glu704fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Glu745fs Likely pathogenic ★★ same condition
CEP164 p.Leu433fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Trp1336fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 c.3278+5_3278+8del Uncertain significance ★★ same condition
CEP164 p.Glu745del 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-arg897fs (accessed [today's date]).

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