Is CTCF p.Pro696= (c.2088C>T) pathogenic?

CTCF p.Pro696= (c.2088C>T) is classified Likely benign in CTCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-28). Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Pro696= (c.2088C>T)?

CTCF p.Pro696= (c.2088C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTCF p.Pro696= (c.2088C>T) in the general population?

CTCF p.Pro696= (c.2088C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

CTCF p.Pro696=

c.2088C>T · rs371078024 · VCV1206987

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -4.1
Overall
CADD	0.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00422% 68/1,613,284 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0391%	2,560
Remaining individualsnot grpmax-eligible	0.00801%	12,480
East Asiangrpmax	0.00668%	14,961
African / African-American	0.00401%	24,958
European (non-Finnish)	0.00263%	38,065
Admixed American	0.00167%	59,994

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro696=
Coding: c.2088C>T
MANE Select: NM_006565
dbSNP: rs371078024
Type: single nucleotide variant
Location: chr16:67637776 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 696: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg368Cys Pathogenic ★★ same condition
CTCF p.Pro378Leu Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg277Gln Uncertain significance ★★ ⚠ same condition
CTCF p.Cys299Arg Uncertain significance ★★ ⚠ same condition
CTCF p.Gly597Arg Uncertain significance ★★ ⚠ same condition
CTCF p.Gly657Arg Uncertain significance ★★ ⚠ same condition
CTCF p.Ile511Val 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-pro696 (accessed [today's date]).

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