Is CTCF p.Arg470His (c.1409G>A) pathogenic?

CTCF p.Arg470His (c.1409G>A) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-06). AlphaMissense: likely pathogenic (0.8199); Very rare (popmax 0.00137%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Arg470His (c.1409G>A)?

CTCF p.Arg470His (c.1409G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTCF p.Arg470His (c.1409G>A) in the general population?

CTCF p.Arg470His (c.1409G>A) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about CTCF p.Arg470His (c.1409G>A)?

AlphaMissense predicts likely pathogenic (score 0.8199) — an in-silico prediction, not a clinical call.

CTCF p.Arg470His

c.1409G>A · rs1259626314 · VCV986078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8199	likely pathogenic
REVEL	0.369	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 7,856 bp · p 2.7e-14 · regional, not allelic
Overall
CADD	34.0	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% African / African-American · 1/72,966 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000191% 3/1,566,814 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	72,966
European (non-Finnish)	0.000173%	577,808

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.Arg470His
Coding: c.1409G>A
MANE Select: NM_006565
dbSNP: rs1259626314
Type: single nucleotide variant
Location: chr16:67626606 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 470: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); a β-strand

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 c.782-1G>C Pathogenic/Likely pathogenic ★★ same condition
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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-arg470his (accessed [today's date]).

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