Is CEP164 p.Pro495fs (c.1481dup) pathogenic?

CEP164 p.Pro495fs (c.1481dup) is classified Pathogenic/Likely pathogenic in CEP164 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-27). Very rare (popmax 0.00899%, eas); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Pro495fs (c.1481dup)?

CEP164 p.Pro495fs (c.1481dup) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Pro495fs (c.1481dup) in the general population?

CEP164 p.Pro495fs (c.1481dup) is very rare (popmax 0.00899%, eas) (gnomAD).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Pro495fs

c.1481dup · rs752518735 · VCV1009382

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00899%, eas)

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 13 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -0.84, phastCons 0.99
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 0.00899% East Asian · 4/44,470 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.0025% 40/1,602,736 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0271%	3,696
East Asiangrpmax	0.00899%	11,117
Admixed American	0.0051%	19,613
Remaining individualsnot grpmax-eligible	0.00161%	61,984
African / African-American	0.00134%	74,654
European (non-Finnish)	0.00119%	83,912

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.Pro495fs
Coding: c.1481dup
MANE Select: NM_014956
dbSNP: rs752518735
Type: Duplication
Location: chr11:117381770 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 495: the 'disordered' region

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.Pro495Arg Benign/Likely benign ★★ same residue
CEP164 p.Pro495Thr Uncertain significance ★ ⚠ same residue
CEP164 p.Gln1014fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Glu557fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Glu846fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Gly250_Asp251insTer Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Lys113fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 p.Lys128fs 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/cep164-p-pro495fs (accessed [today's date]).

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