Is CTCF p.Gln676Arg (c.2027A>G) pathogenic?

CTCF p.Gln676Arg (c.2027A>G) is classified Conflicting classifications of pathogenicity in CTCF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-08). AlphaMissense: likely benign (0.185); Ultra-rare (popmax 0.0296%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Gln676Arg (c.2027A>G)?

CTCF p.Gln676Arg (c.2027A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CTCF p.Gln676Arg (c.2027A>G) in the general population?

CTCF p.Gln676Arg (c.2027A>G) is ultra-rare (popmax 0.0296%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Gln676Arg (c.2027A>G)?

AlphaMissense predicts likely benign (score 0.185) — an in-silico prediction, not a clinical call.

CTCF p.Gln676Arg

c.2027A>G · rs143508499 · VCV1336483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.185 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.185	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.61	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, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 8,396 bp · p 0.23 · regional, not allelic
Overall
CADD	23.6	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 0.0296% European (non-Finnish) · 349/1,179,754 alleles

Filtering AF 0.027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.0231% 372/1,613,552 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0296%	3,380
Remaining individualsnot grpmax-eligible	0.0208%	4,804
Finnishnot grpmax-eligible	0.00781%	12,808
African / African-American	0.00668%	14,979

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.Gln676Arg
Coding: c.2027A>G
MANE Select: NM_006565
dbSNP: rs143508499
Type: single nucleotide variant
Location: chr16:67637715 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 676: 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

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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-gln676arg (accessed [today's date]).

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