Is CTCF p.Ser558= (c.1674T>G) pathogenic?

CTCF p.Ser558= (c.1674T>G) is classified Likely benign in CTCF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-05). Ultra-rare (popmax 0.0779%, sas); Associated with CTCF-related disorder.

What condition is associated with CTCF p.Ser558= (c.1674T>G)?

CTCF p.Ser558= (c.1674T>G) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Ser558= (c.1674T>G) in the general population?

CTCF p.Ser558= (c.1674T>G) is ultra-rare (popmax 0.0779%, sas) (gnomAD).

CTCF p.Ser558=

c.1674T>G · rs774149940 · VCV3052523

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0779%, sas)

Conditions

CTCF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -1.1, phastCons 0.99
Overall
CADD	8.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0779% South Asian · 71/91,090 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00446% 72/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0779%	1,283
European (non-Finnish)	8.47e-05%	1,180,032

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.Ser558=
Coding: c.1674T>G
MANE Select: NM_006565
dbSNP: rs774149940
Type: single nucleotide variant
Location: chr16:67628525 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 558: 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

CTCF-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTCF p.Arg368His Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Glu187Ter Likely pathogenic ★ same condition
CTCF p.Leu366Phe Likely pathogenic ★ same condition
CTCF p.Met329Val Likely pathogenic ★ same condition
CTCF p.Ala697Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
CTCF p.Cys472Arg Uncertain significance ★ ⚠ same condition
CTCF p.Ala669Thr Uncertain significance ⚠ same condition
CTCF p.Gly375Glu 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-ser558 (accessed [today's date]).

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