Is CEP164 p.Asp1065fs (c.3193del) pathogenic?

CEP164 p.Asp1065fs (c.3193del) is classified Pathogenic in CEP164 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-10). Very rare (popmax 0.00062%, nfe); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Asp1065fs (c.3193del)?

CEP164 p.Asp1065fs (c.3193del) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Asp1065fs (c.3193del) in the general population?

CEP164 p.Asp1065fs (c.3193del) is very rare (popmax 0.00062%, nfe) (gnomAD).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Asp1065fs

c.3193del · rs1249398531 · VCV2153417

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00062%, 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 25 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.1	GERP 0.16, phastCons 1
Overall
CADD	27.1	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 0.00062% European (non-Finnish) · 7/1,128,888 alleles

Filtering AF 0.000258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000587% 9/1,532,528 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00176%	56,758
Remaining individualsnot grpmax-eligible	0.00174%	57,406
European (non-Finnish)grpmax	0.00062%	161,270

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp1065fs
Coding: c.3193del
MANE Select: NM_014956
dbSNP: rs1249398531
Type: Deletion
Location: chr11:117396156 (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.Arg897fs Pathogenic/Likely pathogenic ★★ same condition
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
CEP164 p.Gly215del 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-asp1065fs (accessed [today's date]).

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