CTCF c.1357+4A>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
CTCF-related neurodevelopmental disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.40 | donor loss · deltas |
| Pangolin | Δ0.29 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 20.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CTCF
- Coding
- c.1357+4A>C
- MANE Select
- NM_006565
- Type
- single nucleotide variant
- Location
- chr16:67621595 (GRCh38)
- Gene constraint
- LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.45 · 21 PDB
Disease context
CTCF-related neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor CTCF-related neurodevelopmental disorder (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Antenatal, Childhood, Infancy, Neonatal
Similar variants
- CTCF c.782-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CTCF c.782-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CTCF c.782-2A>T Pathogenic ★★ same condition
- CTCF p.Arg283His Likely pathogenic ★★ same condition
- CTCF p.Arg342Cys Pathogenic/Likely pathogenic ★★ same condition
- CTCF p.Arg342His Pathogenic/Likely pathogenic ★★ same condition
- CTCF p.Arg368Cys Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctcf-c-1357-plus-4a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown