Is CTCF p.Glu691del (c.2070_2072del) pathogenic?

CTCF p.Glu691del (c.20702072del) is classified Uncertain significance in CTCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-01). Very rare (popmax 0.000169%, nfe).

How common is CTCF p.Glu691del (c.2070_2072del) in the general population?

CTCF p.Glu691del (c.2070_2072del) is very rare (popmax 0.000169%, nfe) (gnomAD).

CTCF p.Glu691del

c.2070_2072del · rs2142889112 · VCV1307079

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,028 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,514 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.Glu691del
Coding: c.2070_2072del
MANE Select: NM_006565
dbSNP: rs2142889112
Type: Deletion
Location: chr16:67637757 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 691: the 'disordered' region; a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance)

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

Similar variants

CTCF p.Lys206fs Pathogenic ★★ same type
CTCF p.Lys258fs Pathogenic ★★ same type
CTCF p.Val556_Cys557insTer Pathogenic ★★ same type
CTCF p.Asn241fs Likely pathogenic ★ same type
CTCF p.Glu230fs Pathogenic ★ same type
CTCF p.Gly335fs Likely pathogenic ★ same type
CTCF p.Ile426_His430del Likely pathogenic ★ same type
CTCF p.Leu98fs Pathogenic ★ same type

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-glu691del (accessed [today's date]).

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