Is CCDC39 p.Ser888fs (c.2660dup) pathogenic?

CCDC39 p.Ser888fs (c.2660dup) is classified Benign/Likely benign in CCDC39 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.19%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Ser888fs (c.2660dup)?

CCDC39 p.Ser888fs (c.2660dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Ser888fs (c.2660dup) in the general population?

CCDC39 p.Ser888fs (c.2660dup) is low-frequency (popmax 1.19%, 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.Ser888fs

c.2660dup · rs200353947 · VCV194994

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, 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	escapes	premature termination codon within the last 50 nt of the penultimate exon (19 of 20, 8 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 -4.5	GERP -5.5
Overall
CADD	23.8	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 1.19% European (non-Finnish) · 14,023/1,179,326 alleles

Filtering AF 1.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 1.02% 16,466/1,613,166 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.66%	60
European (non-Finnish)grpmax	1.19%	84
Remaining individualsnot grpmax-eligible	0.874%	114
Ashkenazi Jewishnot grpmax-eligible	0.751%	133
Middle Eastern	0.562%	178
Admixed American	0.479%	209
African / African-American	0.185%	539
South Asian	0.168%	595

Finnish 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.Ser888fs
Coding: c.2660dup
MANE Select: NM_181426
dbSNP: rs200353947
Type: Duplication
Location: chr3:180616289 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.23 · 1 PDB
Residue 888: the 'disordered' region

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.Ser888= Likely benign ★ 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.Gln438fs Pathogenic ★ same condition
CCDC39 p.Glu198fs Pathogenic ★ same condition
CCDC39 p.Glu372fs 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-ser888fs (accessed [today's date]).

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