CFAP57

Chr 1AR

cilia and flagella associated protein 57

Also known as: SPGF95, VWS2, WDR65

NCBI Gene: 149465 ENSG00000243710 UniProt: Q96MR6 OMIM: 614259

This protein associates with components of the nexin-dynein regulatory complex and functions as an inner dynein arm hub that regulates ciliary and flagellar motility. Mutations cause spermatogenic failure, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member is thought to function in craniofacial development, possibly in the fusion of lip and palate. A missense mutation in this gene is associated with Van der Woude syndrome 2. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.111 OMIM phenotype

Clinical Summary— CFAP57

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Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

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

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 103 VUS of 161 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CFAP57

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 1.09

OE 0.78 (0.56–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.45Z-score

OE missense 0.94 (0.86–1.02)

361 obs / 385.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.56–1.11)

0≤0.351.4

Missense OE?0.94 (0.86–1.02)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 22 / 28.2Missense obs/exp: 361 / 385.9Syn Z: 0.61

This gene — mechanism propensity

0.7228th %ile

GOF

0.5170th %ile

LOF

0.3067th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS103

Likely Benign29

Benign5

Conflicting2

Pathogenic

Likely Pathogenic

103

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	3	0	0	0	3
VUS	0	101	2	0	103
Likely Benign	1	15	2	11	29
Benign	0	4	1	0	5
Conflicting	—				2
Total	5	120	5	11	143

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CFAP57 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →