Is CTCF p.Arg457Ter (c.1369C>T) pathogenic?

CTCF p.Arg457Ter (c.1369C>T) is classified Pathogenic in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-27). Very rare (popmax 8.97e-05%, nfe).

How common is CTCF p.Arg457Ter (c.1369C>T) in the general population?

CTCF p.Arg457Ter (c.1369C>T) is very rare (popmax 8.97e-05%, nfe) (gnomAD).

CTCF p.Arg457Ter

c.1369C>T · rs763765410 · VCV2104020

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.97e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.009	GERP -1.4, phastCons 0.73
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.97e-05% European (non-Finnish) · 1/1,114,344 alleles

Overall 7.46e-05% 1/1,340,752 alleles · very rare

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.Arg457Ter
Coding: c.1369C>T
MANE Select: NM_006565
dbSNP: rs763765410
Type: single nucleotide variant
Location: chr16:67626566 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 457: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); an α-helix

Full CTCF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTCF p.Arg457Gln Uncertain significance ★ ⚠ same residue
CTCF p.Arg457Gly 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

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-arg457ter (accessed [today's date]).

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