Is CCNO p.Gln88fs (c.258_262dup) pathogenic?

CCNO p.Gln88fs (c.258262dup) is classified Pathogenic in CCNO (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-07-22). Ultra-rare (popmax 0.0502%, mid); Associated with CCNO-related disorder.

What condition is associated with CCNO p.Gln88fs (c.258_262dup)?

CCNO p.Gln88fs (c.258_262dup) is associated with CCNO-related disorder, primary ciliary dyskinesia 29, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Gln88fs (c.258_262dup) in the general population?

CCNO p.Gln88fs (c.258_262dup) is ultra-rare (popmax 0.0502%, mid) (gnomAD).

CCNO p.Gln88fs

c.258_262dup · rs587777499 · VCV139600

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0502%, mid)

Conditions

CCNO-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 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP 0.46, phastCons 0.024
Overall
CADD	26.5	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 0.0502% Middle Eastern · 3/5,982 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0185%

Overall 0.011% 175/1,589,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0502%	1,994
East Asian	0.0363%	2,755
Remaining individualsnot grpmax-eligible	0.013%	7,703
South Asian	0.0113%	8,820
European (non-Finnish)	0.0108%	9,289
African / African-American	0.0107%	9,352
Admixed American	0.00355%	28,136
Finnishnot grpmax-eligible	0.00344%	29,079

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: CCNO
Protein: p.Gln88fs
Coding: c.258_262dup
MANE Select: NM_021147
dbSNP: rs587777499
Type: Microsatellite
Location: chr5:55233261 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 88: the 'disordered' region

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

Disease context

CCNO-related disorder

Also linked: primary ciliary dyskinesia 29 primary ciliary dyskinesia

Similar variants

CCNO p.Gln88His Likely benign ★ same residue
CCNO p.Leu161fs Pathogenic ★ same condition
CCNO p.Phe208fs Pathogenic ★ same condition
CCNO p.Gln103Ter Pathogenic ★★ same condition
CCNO p.Gly85fs Pathogenic ★★ same condition
CCNO p.Val143fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Val180fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Val90fs 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/ccno-p-gln88fs (accessed [today's date]).

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