Is CTCF p.Arg283His (c.848G>A) pathogenic?

CTCF p.Arg283His (c.848G>A) is classified Likely pathogenic in CTCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-21). AlphaMissense: likely pathogenic (0.9988); Very rare (popmax 8.47e-05%, nfe); Associated with CTCF-related neurodevelopmental disorder.

What condition is associated with CTCF p.Arg283His (c.848G>A)?

CTCF p.Arg283His (c.848G>A) is associated with CTCF-related neurodevelopmental disorder (ClinVar).

How common is CTCF p.Arg283His (c.848G>A) in the general population?

CTCF p.Arg283His (c.848G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is CTCF-related neurodevelopmental disorder inherited?

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

What do computational predictors say about CTCF p.Arg283His (c.848G>A)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

CTCF p.Arg283His

c.848G>A · rs1567609067 · VCV562205

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTCF-related neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic ✓ concordant with ClinVar
REVEL	0.475	indeterminate
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 10 kb · p 3.4e-38 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,998 alleles

Overall 6.84e-05% 1/1,461,864 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTCF
Protein: p.Arg283His
Coding: c.848G>A
MANE Select: NM_006565
dbSNP: rs1567609067
Type: single nucleotide variant
Location: chr16:67612017 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 283: 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.Arg283Cys Likely pathogenic ★ 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.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-p-arg283his (accessed [today's date]).

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