Is CTCF p.Phe550= (c.1650C>T) pathogenic?

CTCF p.Phe550= (c.1650C>T) is classified Likely benign in CTCF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-07). Ultra-rare (popmax 0.015%, amr); Associated with CTCF-related disorder.

What condition is associated with CTCF p.Phe550= (c.1650C>T)?

CTCF p.Phe550= (c.1650C>T) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Phe550= (c.1650C>T) in the general population?

CTCF p.Phe550= (c.1650C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

CTCF p.Phe550=

c.1650C>T · rs373346637 · VCV3046838

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

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 -0.059	GERP -4.1, phastCons 0.89
Overall
CADD	9.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,996 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00161% 26/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
East Asian	0.00445%	22,449
African / African-American	0.00267%	37,470
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00102%	98,338

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.Phe550=
Coding: c.1650C>T
MANE Select: NM_006565
dbSNP: rs373346637
Type: single nucleotide variant
Location: chr16:67628501 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 550: 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

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-phe550 (accessed [today's date]).

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