Is CTCF p.Arg396fs (c.1186dup) pathogenic?

CTCF p.Arg396fs (c.1186dup) is classified Pathogenic in CTCF (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-21). Ultra-rare (gnomAD MAF 2.882e-06); Associated with CTCF-related neurodevelopmental disorder.

What condition is associated with CTCF p.Arg396fs (c.1186dup)?

CTCF p.Arg396fs (c.1186dup) is associated with CTCF-related neurodevelopmental disorder (ClinVar).

How common is CTCF p.Arg396fs (c.1186dup) in the general population?

CTCF p.Arg396fs (c.1186dup) is ultra-rare (gnomAD MAF 2.882e-06) (gnomAD).

How is CTCF-related neurodevelopmental disorder inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CTCF p.Arg396fs

c.1186dup · rs879255571 · VCV88637

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 2.882e-06)

Conditions

CTCF-related neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP -0.31, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000288% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CTCF
Protein: p.Arg396fs
Coding: c.1186dup
MANE Select: NM_006565
dbSNP: rs879255571
Type: Duplication
Location: chr16:67620792 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 396: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); an α-helix

Full CTCF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CTCF-related neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CTCF-related neurodevelopmental disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Childhood, Infancy, Neonatal

Similar variants

CTCF p.Ala148fs Likely pathogenic ★ same condition
CTCF p.Asp290fs Likely pathogenic ★ same condition
CTCF p.Gly111fs Pathogenic ★ same condition
CTCF p.His541fs Pathogenic ★ same condition
CTCF p.Tyr25Ter Likely pathogenic ★ same condition
CTCF p.Val126fs Pathogenic ★ same condition
CTCF p.Val225fs Likely pathogenic ★ same condition
CTCF p.Val50fs 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-p-arg396fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown