CFAP92

Chr 3

cilia and flagella associated protein 92 (putative)

Also known as: FAP92, KIAA1257

NCBI Gene: 57501 ENSG00000114656 UniProt: Q9ULG3

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.34

Clinical Summary— CFAP92

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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

21 unique Pathogenic / Likely Pathogenic· 163 VUS of 295 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.50

OE 0.87 (0.58–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.56Z-score

OE missense 0.90 (0.80–1.01)

203 obs / 226.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.58–1.34)

0≤0.351.4

Missense OE?0.90 (0.80–1.01)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 15 / 17.2Missense obs/exp: 203 / 226.6Syn Z: 0.53

This gene — mechanism propensity

0.6064th %ile

GOF

0.6345th %ile

LOF

0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

LOF90% of P/LP variants are LoF

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic18

VUS163

Likely Benign92

Benign1

Conflicting4

Pathogenic

Likely Pathogenic

163

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	16	2	0	0	18
VUS	2	152	3	6	163
Likely Benign	1	8	46	37	92
Benign	0	0	1	0	1
Conflicting	—				4
Total	22	162	50	43	281

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

View in ClinVar →

2 pathogenic / likely-pathogenic (of 5) ClinVar copy-number / structural variants overlap CFAP92 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →