Is CCDC39 p.Arg96Ter (c.286C>T) pathogenic?

CCDC39 p.Arg96Ter (c.286C>T) is classified Pathogenic in CCDC39 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Very rare (popmax 0.00229%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Arg96Ter (c.286C>T)?

CCDC39 p.Arg96Ter (c.286C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Arg96Ter (c.286C>T) in the general population?

CCDC39 p.Arg96Ter (c.286C>T) is very rare (popmax 0.00229%, 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.Arg96Ter

c.286C>T · rs778577109 · VCV565699

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00229%, eas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1
Overall
CADD	36.0	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 0.00229% East Asian · 1/43,762 alleles

Filtering AF 0.000297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.000697% 11/1,577,474 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00229%	43,762
Remaining individualsnot grpmax-eligible	0.00163%	61,200
South Asian	0.00116%	86,270
European (non-Finnish)	0.00069%	144,965

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.Arg96Ter
Coding: c.286C>T
MANE Select: NM_181426
dbSNP: rs778577109
Type: single nucleotide variant
Location: chr3:180661932 (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 c.1034+2T>A Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1167+1261A>G Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1362+1G>A Likely pathogenic ★★ same condition
CCDC39 c.1999-2A>T Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.210+2T>C Pathogenic ★★ same condition
CCDC39 c.357+1G>C Pathogenic ★★ same condition
CCDC39 c.516+1G>A Likely pathogenic ★★ same condition
CCDC39 c.610-2A>G 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-arg96ter (accessed [today's date]).

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