Is CTCF p.Ala697Thr (c.2089G>A) pathogenic?

CTCF p.Ala697Thr (c.2089G>A) is classified Conflicting classifications of pathogenicity in CTCF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-22). AlphaMissense: likely benign (0.0728); Very rare (popmax 0.00668%, eas); Associated with CTCF-related disorder.

What condition is associated with CTCF p.Ala697Thr (c.2089G>A)?

CTCF p.Ala697Thr (c.2089G>A) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Ala697Thr (c.2089G>A) in the general population?

CTCF p.Ala697Thr (c.2089G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CTCF p.Ala697Thr (c.2089G>A)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

CTCF p.Ala697Thr

c.2089G>A · rs201916739 · VCV589165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTCF-related disorder

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.83, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 8,396 bp · p 0.23 · regional, not allelic
Overall
CADD	14.18	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 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00223% 36/1,613,310 alleles · very rare exomes 33/1,461,154 · genomes 3/152,156 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.00481%	20,800
European (non-Finnish)	0.00237%	42,143
Admixed American	0.00167%	59,996
South Asian	0.0011%	91,036

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.Ala697Thr
Coding: c.2089G>A
MANE Select: NM_006565
dbSNP: rs201916739
Type: single nucleotide variant
Location: chr16:67637777 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 697: 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

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

Similar variants

CTCF p.Ala697Ser Uncertain significance ★ ⚠ same residue
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.Cys472Arg Uncertain significance ★ ⚠ same condition
CTCF p.Ala669Thr Uncertain significance ⚠ same condition
CTCF p.Gly375Glu 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-ala697thr (accessed [today's date]).

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