Is CEP164 p.Lys128fs (c.381dup) pathogenic?

CEP164 p.Lys128fs (c.381dup) is classified Pathogenic/Likely pathogenic in CEP164 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-25). Very rare (popmax 0.0036%, nfe); Associated with CEP164-related disorder.

What condition is associated with CEP164 p.Lys128fs (c.381dup)?

CEP164 p.Lys128fs (c.381dup) is associated with CEP164-related disorder, nephronophthisis 15, inherited retinal dystrophy (ClinVar).

How common is CEP164 p.Lys128fs (c.381dup) in the general population?

CEP164 p.Lys128fs (c.381dup) is very rare (popmax 0.0036%, nfe) (gnomAD).

CEP164 p.Lys128fs

c.381dup · rs747914869 · VCV581067

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0036%, nfe)

Conditions

CEP164-related disorder

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 5 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 1.7, phastCons 1
Overall
CADD	27.3	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 0.0036% European (non-Finnish) · 42/1,166,310 alleles

Filtering AF 0.0027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.00284% 45/1,585,780 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0036%	27,769
East Asian	0.00228%	43,812
Admixed American	0.00183%	54,526
African / African-American	0.00136%	73,498

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.Lys128fs
Coding: c.381dup
MANE Select: NM_014956
dbSNP: rs747914869
Type: Duplication
Location: chr11:117351969 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 128: the 'interaction with atrip' region; the 'disordered' region

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

Disease context

CEP164-related disorder

Also linked: nephronophthisis 15 inherited retinal dystrophy

Similar variants

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.Pro495fs Pathogenic/Likely pathogenic ★★ same condition
CEP164 c.2834_2844+13dup Uncertain significance ★★ same condition
CEP164 p.Glu1421fs 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-lys128fs (accessed [today's date]).

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