CFAP69

protein-coding

cilia and flagella associated protein 69, the group of Armadillo like helical domain containing|Cilia and flagella associated

Gene summary

Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C7orf63

MANE transcript

NM_001039706.3

Inheritance

ClinVar variants

P:6U:127B:26

Top phenotype

Spermatogenic failure 24

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr7:90,245,174-90,311,063

External References & Databases

Ensembl (ENSG00000105792)

Transcript & Mutation Effects

hg38 • Region Span ~65.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

spermatogenic failure 24LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054728

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spermatogenic failure 24AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29606301

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP69 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 17

CFAP69-related disorderTotal: 11

Spermatogenic failure 24Total: 4

Susceptibility to severe COVID-19Total: 1

Non-syndromic male infertility due to sperm motility disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039706.3. 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			1 clinvar	5 clinvar	4 clinvar	10
missense			124 clinvar	14 clinvar	3 clinvar	141
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	4	2	127	19	7	159

Highest pathogenic variant AF is 0.000105110244

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039706.3	RefSeq	NP_001034795.2	23	MANE Select
ENST00000389297.8	Ensembl	ENSP00000373948.4	23	MANE Select
NM_001160138.2	RefSeq	NP_001153610.1	23	Standard
NM_001363438.1	RefSeq	NP_001350367.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spermatogenesis
sensory perception of smell
cell differentiation
olfactory behavior
positive regulation of flagellated sperm motility

Cellular Component

cytoplasm
sperm midpiece
non-motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389297
Coding exons: 23
Length: 65890
Individuals with no LoFs: 124691
Homozygous LoFs: 0
Heterozygous LoFs: 102
Defined: 124793
p: 0.000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.371	430	452	0.951	0.0000215	6168
Missense (PolyPhen)		131	152.58	0.85857		2159
Synonymous	0.594	145	154	0.939	0.00000747	1679
Loss of Function	3.82	21	50.2	0.418	0.00000246	684

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00045	rare
Latino/Admixed American	0.00064	0.00049	rare
Ashkenazi Jewish	0.0022	0.0021	notable
East Asian	0.00041	0.00039	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00041	0.00036	rare
South Asian	0.00014	0.00013	rare
Other	0.00076	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: 0.25
RVIS percentile EVS: 69.62

Essentials

Essential (gene trap): N