Is CTCF p.Tyr502fs (c.1502_1503dup) pathogenic?

CTCF p.Tyr502fs (c.15021503dup) is classified Likely pathogenic in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-01). Absent from gnomAD; Associated with acute megakaryoblastic leukemia in down syndrome.

What condition is associated with CTCF p.Tyr502fs (c.1502_1503dup)?

CTCF p.Tyr502fs (c.1502_1503dup) is associated with acute megakaryoblastic leukemia in down syndrome (ClinVar).

How common is CTCF p.Tyr502fs (c.1502_1503dup) in the general population?

CTCF p.Tyr502fs (c.1502_1503dup) is absent from gnomAD (gnomAD).

How is Acute megakaryoblastic leukemia inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CTCF p.Tyr502fs

c.1502_1503dup · rs2052291685 · VCV998068

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

acute megakaryoblastic leukemia in down syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTCF
Protein: p.Tyr502fs
Coding: c.1502_1503dup
MANE Select: NM_006565
dbSNP: rs2052291685
Type: Duplication
Location: chr16:67626698 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 502: 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

acute megakaryoblastic leukemia in down syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acute megakaryoblastic leukemia (Orphanet):

Inheritance: Not applicable
Onset: Adult, Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

CTCF p.Tyr502= Likely benign ★ same residue
CTCF p.Asp547fs Likely pathogenic ★ same condition
CTCF p.Thr204fs Pathogenic ★★ same type
CTCF p.Ala148fs Likely pathogenic ★ same type
CTCF p.Arg396fs Pathogenic ★ same type
CTCF p.Arg596fs Pathogenic ★ same type
CTCF p.Asp290fs Likely pathogenic ★ same type
CTCF p.Cys353fs 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-tyr502fs (accessed [today's date]).

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