Is CTCF p.Arg567Trp (c.1699C>T) pathogenic?

CTCF p.Arg567Trp (c.1699C>T) is classified Pathogenic/Likely pathogenic in CTCF (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-09-02). AlphaMissense: likely pathogenic (0.9576); Absent from gnomAD v4.1; Associated with CTCF-related syndromic intellectual disability.

What condition is associated with CTCF p.Arg567Trp (c.1699C>T)?

CTCF p.Arg567Trp (c.1699C>T) is associated with CTCF-related syndromic intellectual disability, intellectual disability, CTCF-related neurodevelopmental disorder (ClinVar).

How common is CTCF p.Arg567Trp (c.1699C>T) in the general population?

CTCF p.Arg567Trp (c.1699C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Arg567Trp (c.1699C>T)?

AlphaMissense predicts likely pathogenic (score 0.9576) — an in-silico prediction, not a clinical call.

CTCF p.Arg567Trp

c.1699C>T · rs879255516 · VCV88638

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.9576 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTCF-related syndromic intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9576	likely pathogenic ✓ concordant with ClinVar
REVEL	0.467	indeterminate
SaProt	LLR -11.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.17, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 7,856 bp · p 2.7e-14 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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
Protein: p.Arg567Trp
Coding: c.1699C>T
MANE Select: NM_006565
dbSNP: rs879255516
Type: single nucleotide variant
Location: chr16:67628550 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 567: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); a UniProt-annotated variant site (in mrd21); an α-helix

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

Disease context

CTCF-related syndromic intellectual disability

Also linked: intellectual disability CTCF-related neurodevelopmental disorder

Similar variants

CTCF p.Arg567Leu Likely benign ★ same residue
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

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-arg567trp (accessed [today's date]).

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