Is CCDC39 p.Glu731fs (c.2190del) pathogenic?

CCDC39 p.Glu731fs (c.2190del) is classified Pathogenic in CCDC39 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-29). Very rare (popmax 0.00149%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Glu731fs (c.2190del)?

CCDC39 p.Glu731fs (c.2190del) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 14 (ClinVar).

How common is CCDC39 p.Glu731fs (c.2190del) in the general population?

CCDC39 p.Glu731fs (c.2190del) is very rare (popmax 0.00149%, nfe) (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.Glu731fs

c.2190del · rs587778820 · VCV65950

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00149%, nfe)

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 16 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Overall
CADD	32.0	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 0.00149% European (non-Finnish) · 17/1,138,298 alleles

Filtering AF 0.00091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000744%

Overall 0.00123% 19/1,539,432 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,476
Remaining individualsnot grpmax-eligible	0.00168%	59,638
European (non-Finnish)grpmax	0.00149%	66,959

Ashkenazi Jewish 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: CCDC39
Protein: p.Glu731fs
Coding: c.2190del
MANE Select: NM_181426
dbSNP: rs587778820
Type: Deletion
Location: chr3:180619334 (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 c.610_613del Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Arg542fs Pathogenic ★★ same condition
CCDC39 p.Arg615_Tyr616insTer Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Cys680fs Pathogenic ★★ same condition
CCDC39 p.Cys73fs Pathogenic ★★ same condition
CCDC39 p.Gln833fs Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Glu655fs Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Ile624fs 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-glu731fs (accessed [today's date]).

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