Is CCDC39 p.Ser496fs (c.1485dup) pathogenic?

CCDC39 p.Ser496fs (c.1485dup) is classified Pathogenic in CCDC39 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). Very rare (popmax 0.00223%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Ser496fs (c.1485dup)?

CCDC39 p.Ser496fs (c.1485dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Ser496fs (c.1485dup) in the general population?

CCDC39 p.Ser496fs (c.1485dup) is very rare (popmax 0.00223%, eas) (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.Ser496fs

c.1485dup · rs751239231 · VCV1069445

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.83, phastCons 0.94

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,746 alleles

Overall 6.86e-05% 1/1,457,382 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.Ser496fs
Coding: c.1485dup
MANE Select: NM_181426
dbSNP: rs751239231
Type: Duplication
Location: chr3:180647120 (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 — 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 p.Ser496Thr Uncertain significance ★★ ⚠ same residue
CCDC39 p.Glu627fs Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Val934_Lys935insVal Uncertain significance ★★ same condition
CCDC39 c.1363-14_1363-13dup Benign/Likely benign ★★ same condition
CCDC39 c.1363-23dup Benign ★★ same condition
CCDC39 p.Ser888fs Benign/Likely benign ★★ same condition
CCDC39 p.Gln438fs Pathogenic ★ same condition
CCDC39 p.Glu198fs 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-ser496fs (accessed [today's date]).

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