Reported in medical literature
~31
approximately 31 cases
These are people described in published studies and case reports. This is not a worldwide patient count; many diagnosed families have never been included in a publication. [1] [2]
CLTC variants in ClinVar
1,313
1,313 submissions (as of September, 2026)
ClinVar contains submitted CLTC variant records, including 85 Pathogenic, 79 Likely Pathogenic, and 552 Variants of Uncertain Significance. ClinVar counts variants and submissions—not unique patients. [3]
Conservative pathogenic estimate
approximately 219
This includes all Pathogenic and Likely Pathogenic entries plus 10% of the VUS entries. It is a rough diagnostic floor, not an incidence rate or patient census.
Broad Institute GenIE estimates
GenIE estimates how often new de novo CLTC variation arises per 100,000 births. [4]
Total de novo variation
5.634
per 100,000 births
Missense variation
5.077
per 100,000 births
Loss-of-function variation
0.557
per 100,000 births
Total rate in familiar terms
approximately 1 in 17,750 births
Estimate annual incidence by country
Choose a country to apply the Broad GenIE rates to its estimated number of births each year. The calculator shows modelled new de novo CLTC variation, not the number of diagnosed patients or everyone living with CLTC-ID.
Broad GenIE incidence calculator
Total de novo variation
5.634 per 100,000 births
~200
Estimated newborns per year with new de novo CLTC variation.
Missense variation
5.077 per 100,000 births
~180
Estimated newborns per year with de novo missense variation.
Loss-of-function variation
0.557 per 100,000 births
~20
Estimated newborns per year with de novo loss-of-function variation.
How this is calculated: estimated annual births × Broad GenIE rate ÷ 100,000. Results are modelled estimates of new de novo variation, not diagnosed-patient counts or prevalence.
What these numbers mean
The published literature and ClinVar show only the cases and variants that have been reported. Broad GenIE estimates that new CLTC variation may occur more often than those records suggest, but its result is a modelled incidence estimate—not an upper bound or a count of patients. The difference points to possible under-recognition, but it cannot tell us exactly how many people remain undiagnosed.
Better estimates require standardized information from diagnosed patients, including variant type, symptoms, age, family history, testing history, and geographic background. The goal of this website is to help families, clinicians, and researchers collect that information in a reliable and privacy-conscious way.
Last reviewed: August 2026
References
- [1]↑DeMari J, Mroske C et al. CLTC as a clinically novel gene associated with multiple malformations and developmental delay. Am J Med Genet A. 2016;170(4):958–66. PubMed →
- [2]↑Nabais Sá MJ, de Man SA et al. De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy. Genet Med. 2020;22(4):797–802. PubMed →
- [3]↑NCBI ClinVar — CLTC gene variant submissions (accessed 2026). ClinVar →
- [4]↑Broad Institute GenIE. CLTC incidence dashboard: Genetic Incidence of De Novo Variation (GIDNV). Total 5.634 per 100,000; missense 5.077 per 100,000; loss-of-function 0.557 per 100,000 (accessed 2026). GenIE dashboard →