CFAP46

Chr 10

cilia and flagella associated protein 46

Also known as: C10orf123, C10orf124, C10orf92, C10orf93, TTC40, bA288G11.4, bA288G11.5, bB137A17.2

NCBI Gene: 54777 ENSG00000171811 UniProt: Q8IYW2 OMIM: 618543

The CFAP46 protein is part of the central apparatus of the cilium axoneme and plays a role in cilium movement. Mutations cause primary ciliary dyskinesia with autosomal recessive inheritance. This gene shows moderate constraint against loss-of-function variants, affecting the respiratory system and ciliary function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.69

Clinical Summary— CFAP46

🧬

Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

173 VUS of 242 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.000

Z-score 4.62

OE 0.57 (0.47–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.91Z-score

OE missense 0.86 (0.82–0.90)

1333 obs / 1544.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.47–0.69)

0≤0.351.4

Missense OE?0.86 (0.82–0.90)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 76 / 133.7Missense obs/exp: 1333 / 1544.5Syn Z: 0.51

ClinVar Variant Classifications

242 submitted variants in ClinVar

ClinVar

Classification Summary

VUS173

Likely Benign41

Conflicting1

173

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	172	0	0	173
Likely Benign	0	26	0	15	41
Benign	0	0	0	0	0
Conflicting	—				1
Total	1	198	0	15	215

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

99 pathogenic / likely-pathogenic (of 124) ClinVar copy-number / structural variants overlap CFAP46 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →