Is CTCF p.Cys472Arg (c.1414T>C) pathogenic?

CTCF p.Cys472Arg (c.1414T>C) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with CTCF-related disorder.

What condition is associated with CTCF p.Cys472Arg (c.1414T>C)?

CTCF p.Cys472Arg (c.1414T>C) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Cys472Arg (c.1414T>C) in the general population?

CTCF p.Cys472Arg (c.1414T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Cys472Arg (c.1414T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

CTCF p.Cys472Arg

c.1414T>C · rs2543484586 · VCV2633611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,466)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTCF-related disorder

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 6% in CTCF
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -17.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 7,856 bp · p 2.7e-14 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,569,466). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTCF
Protein: p.Cys472Arg
Coding: c.1414T>C
MANE Select: NM_006565
dbSNP: rs2543484586
Type: single nucleotide variant
Location: chr16:67626611 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 472: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); a β-strand

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

Disease context

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

Similar variants

CTCF p.Arg368His Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Glu187Ter Likely pathogenic ★ same condition
CTCF p.Leu366Phe Likely pathogenic ★ same condition
CTCF p.Met329Val Likely pathogenic ★ same condition
CTCF p.Ala697Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
CTCF p.Ala669Thr Uncertain significance ⚠ same condition
CTCF p.Gly375Glu Uncertain significance ⚠ same condition
CTCF p.Val10Ala Uncertain significance ⚠ 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-cys472arg (accessed [today's date]).

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