Is CCNO p.Asp292fs (c.875_897del) pathogenic?

CCNO p.Asp292fs (c.875897del) is classified Pathogenic in CCNO (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-25). Very rare (popmax 0.005%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with CCNO p.Asp292fs (c.875_897del)?

CCNO p.Asp292fs (c.875_897del) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Asp292fs (c.875_897del) in the general population?

CCNO p.Asp292fs (c.875_897del) is very rare (popmax 0.005%, amr) (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.Asp292fs

c.875_897del · rs1176911729 · VCV861050

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -0.93, phastCons 1
Overall
CADD	34.0	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 0.005% Admixed American · 3/60,012 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,613,554 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,004
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Asp292fs
Coding: c.875_897del
MANE Select: NM_021147
dbSNP: rs1176911729
Type: Deletion
Location: chr5:55231531 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Asn159fs Pathogenic ★ same condition
CCNO p.Gln249fs Pathogenic ★ same condition
CCNO p.Gly56fs Pathogenic ★ same condition
CCNO p.Ile185fs Likely pathogenic ★ same condition
CCNO p.Ser65fs Pathogenic ★ same condition
CCNO c.568-16del Likely benign ★ same condition
CCNO p.Gln103Ter Pathogenic ★★ same condition
CCNO p.Gln88fs 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-asp292fs (accessed [today's date]).

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