Is CTCF p.Gln44Arg (c.131A>G) pathogenic?

CTCF p.Gln44Arg (c.131A>G) is classified Likely benign in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: likely benign (0.1279); Very rare (popmax 0.00137%, nfe).

How common is CTCF p.Gln44Arg (c.131A>G) in the general population?

CTCF p.Gln44Arg (c.131A>G) is very rare (popmax 0.00137%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Gln44Arg (c.131A>G)?

AlphaMissense predicts likely benign (score 0.1279) — an in-silico prediction, not a clinical call.

CTCF p.Gln44Arg

c.131A>G · rs766320761 · VCV1701292

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1279	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -7.89	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 465 bp · p 0.00078 · regional, not allelic
Overall
CADD	21.4	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 0.00137% European (non-Finnish) · 16/1,164,450 alleles

Filtering AF 0.000813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000658%

Overall 0.00471% 75/1,593,494 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.172%	580
Remaining individualsnot grpmax-eligible	0.0146%	6,828
European (non-Finnish)grpmax	0.00137%	72,778

Ashkenazi Jewish 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.Gln44Arg
Coding: c.131A>G
MANE Select: NM_006565
dbSNP: rs766320761
Type: single nucleotide variant
Location: chr16:67610963 (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

Similar variants

CTCF p.Gln44Lys Uncertain significance ★ ⚠ same residue
CTCF c.782-1G>A Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-2A>G Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-2A>T Pathogenic ★★ same type
CTCF p.Arg283His Likely pathogenic ★★ same type
CTCF p.Arg342Cys Pathogenic/Likely pathogenic ★★ same type
CTCF p.Arg342His Pathogenic/Likely 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-gln44arg (accessed [today's date]).

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