Is CCNO p.Val180fs (c.538dup) pathogenic?

CCNO p.Val180fs (c.538dup) is classified Pathogenic/Likely pathogenic in CCNO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-15). Very rare (popmax 0.00602%, nfe); Associated with CCNO-related disorder.

What condition is associated with CCNO p.Val180fs (c.538dup)?

CCNO p.Val180fs (c.538dup) is associated with CCNO-related disorder, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Val180fs (c.538dup) in the general population?

CCNO p.Val180fs (c.538dup) is very rare (popmax 0.00602%, nfe) (gnomAD).

CCNO p.Val180fs

c.538dup · rs774393276 · VCV525368

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (2 of 3, 28 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
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 0.00602% European (non-Finnish) · 71/1,180,004 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00471% 76/1,613,644 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)grpmax	0.00602%	16,620

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.Val180fs
Coding: c.538dup
MANE Select: NM_021147
dbSNP: rs774393276
Type: Duplication
Location: chr5:55232389 (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

CCNO-related disorder

Also linked: primary ciliary dyskinesia

Similar variants

CCNO p.Gly85fs Pathogenic ★★ same condition
CCNO p.Val143fs 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
CCNO p.Val265fs 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-val180fs (accessed [today's date]).

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