Is CCNO p.Val90fs (c.263_267dup) pathogenic?

CCNO p.Val90fs (c.263267dup) is classified Pathogenic in CCNO (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-16). Ultra-rare (popmax 0.0167%, mid); Associated with primary ciliary dyskinesia 29.

What condition is associated with CCNO p.Val90fs (c.263_267dup)?

CCNO p.Val90fs (c.263_267dup) is associated with primary ciliary dyskinesia 29, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Val90fs (c.263_267dup) in the general population?

CCNO p.Val90fs (c.263_267dup) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CCNO p.Val90fs

c.263_267dup · rs587777502 · VCV139603

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

primary ciliary dyskinesia 29

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 -0.18	GERP -3.3
Overall
CADD	15.2	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 0.0167% Middle Eastern · 1/5,974 alleles

Filtering AF 0.00345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0022%

Overall 0.00265% 42/1,586,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,974
Admixed American	0.00896%	11,158
European (non-Finnish)	0.00265%	37,713
South Asian	0.00227%	43,961
East Asian	0.00227%	44,036
Remaining individualsnot grpmax-eligible	0.00162%	61,550
African / African-American	0.00134%	74,822

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.Val90fs
Coding: c.263_267dup
MANE Select: NM_021147
dbSNP: rs587777502
Type: Duplication
Location: chr5:55233256 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06

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

Disease context

primary ciliary dyskinesia 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCNO p.Gly85fs Pathogenic ★★ same condition
CCNO p.Val143fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Val180fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Ala207fs Pathogenic ★ same condition
CCNO p.Arg304fs Pathogenic ★ same condition
CCNO p.Lys110fs Pathogenic ★ same condition
CCNO p.Pro84fs Pathogenic ★ same condition
CCNO p.Val143delinsLeuTer 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/ccno-p-val90fs (accessed [today's date]).

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