Is CTCF p.Gln44Lys (c.130C>A) pathogenic?

CTCF p.Gln44Lys (c.130C>A) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-04). AlphaMissense: likely benign (0.1207); Very rare (popmax 0.00327%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Gln44Lys (c.130C>A)?

CTCF p.Gln44Lys (c.130C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTCF p.Gln44Lys (c.130C>A) in the general population?

CTCF p.Gln44Lys (c.130C>A) is very rare (popmax 0.00327%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Gln44Lys (c.130C>A)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

CTCF p.Gln44Lys

c.130C>A · rs755800964 · VCV1769614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00327%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.23	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 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 465 bp · p 0.00078 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00327% European (non-Finnish) · 38/1,163,846 alleles

Filtering AF 0.00243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00213%

Overall 0.00251% 40/1,592,416 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00327%	30,627
Admixed American	0.00169%	59,046
Remaining individualsnot grpmax-eligible	0.00163%	61,404

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.Gln44Lys
Coding: c.130C>A
MANE Select: NM_006565
dbSNP: rs755800964
Type: single nucleotide variant
Location: chr16:67610962 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 44: 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 p.Gln44Arg Likely benign ★ same residue
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

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-gln44lys (accessed [today's date]).

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