Is CCDC39 p.Glu627fs (c.1876_1877dup) pathogenic?

CCDC39 p.Glu627fs (c.18761877dup) is classified Pathogenic/Likely pathogenic in CCDC39 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-29). Very rare (popmax 0.00134%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Glu627fs (c.1876_1877dup)?

CCDC39 p.Glu627fs (c.1876_1877dup) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 14 (ClinVar).

How common is CCDC39 p.Glu627fs (c.1876_1877dup) in the general population?

CCDC39 p.Glu627fs (c.1876_1877dup) is very rare (popmax 0.00134%, afr) (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.Glu627fs

c.1876_1877dup · rs746728127 · VCV2955469

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 0.00134%, 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 14 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.94	GERP -2.8, phastCons 0.98
Overall
CADD	25.0	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 0.00134% African / African-American · 1/74,622 alleles

Overall 0.000657% 1/152,198 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.Glu627fs
Coding: c.1876_1877dup
MANE Select: NM_181426
dbSNP: rs746728127
Type: Duplication
Location: chr3:180631589 (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

Also linked: primary ciliary dyskinesia 14

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.Ala688fs 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.Arg256fs Likely pathogenic ★ 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-glu627fs (accessed [today's date]).

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