Is CTCF p.Pro640fs (c.1916dup) pathogenic?

CTCF p.Pro640fs (c.1916dup) is classified Pathogenic in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-08-09). Absent from gnomAD.

How common is CTCF p.Pro640fs (c.1916dup) in the general population?

CTCF p.Pro640fs (c.1916dup) is absent from gnomAD (gnomAD).

CTCF p.Pro640fs

c.1916dup · rs1555536759 · VCV546453

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP -0.34, 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.Pro640fs
Coding: c.1916dup
MANE Select: NM_006565
dbSNP: rs1555536759
Type: Duplication
Location: chr16:67636767 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 640: the 'disordered' region; 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

Similar variants

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
CTCF p.Gln106fs Pathogenic ★ same type
CTCF p.Gly111fs 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-pro640fs (accessed [today's date]).

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