Is CCNO p.Val143fs (c.427dup) pathogenic?

CCNO p.Val143fs (c.427dup) is classified Pathogenic/Likely pathogenic in CCNO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-14). Very rare (popmax 0.00133%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCNO p.Val143fs (c.427dup)?

CCNO p.Val143fs (c.427dup) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 29 (ClinVar).

How common is CCNO p.Val143fs (c.427dup) in the general population?

CCNO p.Val143fs (c.427dup) is very rare (popmax 0.00133%, afr) (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.Val143fs

c.427dup · rs1436895387 · VCV951909

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	35.0	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 0.00133% African / African-American · 1/74,938 alleles

Overall 0.000124% 2/1,613,576 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-Americangrpmax	0.00133%	74,938

Remaining individuals 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: CCNO
Protein: p.Val143fs
Coding: c.427dup
MANE Select: NM_021147
dbSNP: rs1436895387
Type: Duplication
Location: chr5:55232500 (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

Also linked: primary ciliary dyskinesia 29

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.Val143delinsLeuTer Likely pathogenic ★ same residue
CCNO p.Gly85fs Pathogenic ★★ same condition
CCNO p.Val180fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Val90fs 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

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-val143fs (accessed [today's date]).

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