Is CCDC39 p.Ala518fs (c.1553_1563del) pathogenic?

CCDC39 p.Ala518fs (c.15531563del) is classified Pathogenic in CCDC39 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Very rare (popmax 7.22e-05%); Associated with primary ciliary dyskinesia 14.

What condition is associated with CCDC39 p.Ala518fs (c.1553_1563del)?

CCDC39 p.Ala518fs (c.1553_1563del) is associated with primary ciliary dyskinesia 14 (ClinVar).

How common is CCDC39 p.Ala518fs (c.1553_1563del) in the general population?

CCDC39 p.Ala518fs (c.1553_1563del) is very rare (popmax 7.22e-05%) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CCDC39 p.Ala518fs

c.1553_1563del · VCV4854737

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 7.22e-05%)

Conditions

primary ciliary dyskinesia 14

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 12 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.22e-05%

Overall 7.22e-05% 1/1,385,474 alleles · very rare

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: CCDC39
Protein: p.Ala518fs
Coding: c.1553_1563del
MANE Select: NM_181426
Type: Deletion
Location: chr3:180644222 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.23 · 1 PDB

Full CCDC39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 14 — 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

CCDC39 c.610_613del Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Arg615_Tyr616insTer Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Cys680fs Pathogenic ★★ same condition
CCDC39 p.Gln833fs Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Glu655fs Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Glu731fs Pathogenic ★★ same condition
CCDC39 p.Ile624fs Pathogenic ★★ same condition
CCDC39 p.Lys25fs Pathogenic/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/ccdc39-p-ala518fs (accessed [today's date]).

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