CFAP126

Chr 1

cilia and flagella associated protein 126

Also known as: C1orf192, Flattop, Fltp

NCBI Gene: 257177 ENSG00000188931 UniProt: Q5VTH2 OMIM: 616119

Predicted to be involved in cilium organization and flagellated sperm motility. Located in several cellular components, including axonemal microtubule; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.69

Clinical Summary— CFAP126

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 26 VUS of 39 total submissions

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?

1.69LOEUF

pLI 0.000

Z-score 0.06

OE 0.98 (0.57–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.71Z-score

OE missense 0.80 (0.66–0.96)

78 obs / 97.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.98 (0.57–1.69)

0≤0.351.4

Missense OE?0.80 (0.66–0.96)

0≤0.61.4

Synonymous OE?0.60

0≤1.21.6

LoF obs/exp: 8 / 8.2Missense obs/exp: 78 / 97.9Syn Z: 1.81

This gene — mechanism propensity

0.76top 25%

GOF

0.7028th %ile

LOF

0.3842th %ile

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

DNprediction above median

GOFprediction 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

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS26

Likely Benign2

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	2	2
Likely Pathogenic	0	0	0
VUS	25	1	26
Likely Benign	2	0	2
Benign	0	0	0
Total	27	3	30

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap CFAP126 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →