CFAP20DC

CFAP20DC was first reported in association with autosomal-recessive primary ciliary dyskinesia in 2025 in a Saudi pediatric patient homozygous for the nonsense variant NM_198463.2:c.508C>T, p.(Arg170Ter), corresponding to NM_001394063.1:c.883C>T, p.(Arg295Ter). A subsequent multicenter study by Gerard et al., 2026 identified 24 affected individuals from 16 families and seven countries with eight distinct biallelic CFAP20DC variants, including nonsense, frameshift, canonical splice-site, multiexon deletion, in-frame deletion alleles, and recurrent p.(Arg295Ter) cases. Affected individuals suffered from chronic and severe airway disease marked by early-age onset of bronchiectasis, predominantly in the middle and lower lungs, and absence of ciliary ultrastructural defects. Case-level evidence reaches the ClinGen maximum of 12 genetic evidence points. Experimental evidence includes enrichment of CFAP20DC expression in deuterosomal cells and functional abnormalities in patient-derived respiratory epithelial cells. Affected cells showed cytoplasmic mislocalization and abnormal orientation of basal bodies, reduced generation of multiple motile cilia, abnormal localization of the basal-foot marker CNTRL, and markedly impaired ciliary particle transport. No convincing contradictory evidence was identified. The combined evidence score is 14.5 points, comprising 12 genetic and 2.5 experimental evidence points.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP20DC variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 8

not providedTotal: 5

Primary ciliary dyskinesiaTotal: 1

Tuberous sclerosis 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394063.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			11 clinvar	2 clinvar	1 clinvar	14
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	16	2	2	20

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394063.1	RefSeq	NP_001380992.1	17	MANE Select
ENST00000482387.7	Ensembl	ENSP00000417122.2	17	MANE Select
NM_001351530.2	RefSeq	NP_001338459.1	16	Standard
NM_001351531.2	RefSeq	NP_001338460.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
zgc:162324	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

zgc:162324

Danio rerio

Structure: otolith

Quality: morphology

abnormal

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295966
Coding exons: 12
Length: 332719
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.363	292	310	0.942	0.0000161	3704
Missense (PolyPhen)		95	91.316	1.0403		1121
Synonymous	0.118	113	115	0.986	0.00000626	1049
Loss of Function	1.90	21	32.7	0.642	0.00000186	354

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00038	0.00036	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.908
RVIS EVS: 0.49
RVIS percentile EVS: 79.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium