Is CCDC39 p.Arg294Gly (c.880A>G) pathogenic?

CCDC39 p.Arg294Gly (c.880A>G) is classified Conflicting classifications of pathogenicity in CCDC39 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). AlphaMissense: ambiguous (0.3593); Rare (popmax 0.423%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Arg294Gly (c.880A>G)?

CCDC39 p.Arg294Gly (c.880A>G) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 14 (ClinVar).

How common is CCDC39 p.Arg294Gly (c.880A>G) in the general population?

CCDC39 p.Arg294Gly (c.880A>G) is rare (popmax 0.423%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CCDC39 p.Arg294Gly (c.880A>G)?

AlphaMissense predicts ambiguous (score 0.3593) — an in-silico prediction, not a clinical call.

CCDC39 p.Arg294Gly

c.880A>G · rs61733577 · VCV344274

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.3593 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.423%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.3593	ambiguous
REVEL	0.428	indeterminate
SaProt	LLR -9.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.46, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 64 kb · p 0.72 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.423% African / African-American · 317/74,916 alleles

Filtering AF 0.385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.37%

Overall 0.0624% 1,005/1,611,292 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.423%	236
European (non-Finnish)	0.0557%	1,797
Remaining individualsnot grpmax-eligible	0.0273%	3,668
Admixed American	0.0234%	4,266
South Asian	0.00111%	90,482

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.Arg294Gly
Coding: c.880A>G
MANE Select: NM_181426
dbSNP: rs61733577
Type: single nucleotide variant
Location: chr3:180654812 (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.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-arg294gly (accessed [today's date]).

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