Is CTCF p.Leu366Phe (c.1098A>C) pathogenic?

CTCF p.Leu366Phe (c.1098A>C) is classified Likely pathogenic in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-14). AlphaMissense: likely pathogenic (0.9948); Absent from gnomAD v4.1; Associated with CTCF-related disorder.

What condition is associated with CTCF p.Leu366Phe (c.1098A>C)?

CTCF p.Leu366Phe (c.1098A>C) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Leu366Phe (c.1098A>C) in the general population?

CTCF p.Leu366Phe (c.1098A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Leu366Phe (c.1098A>C)?

AlphaMissense predicts likely pathogenic (score 0.9948) — an in-silico prediction, not a clinical call.

CTCF p.Leu366Phe

c.1098A>C · rs776804939 · VCV2637200

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9948 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTCF-related disorder

Computational evidence

Protein change
AlphaMissense	0.9948	likely pathogenic ✓ concordant with ClinVar
REVEL	0.436	indeterminate
SaProt	LLR -10.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 10 kb · p 3.4e-38 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTCF
Protein: p.Leu366Phe
Coding: c.1098A>C
MANE Select: NM_006565
dbSNP: rs776804939
Type: single nucleotide variant
Location: chr16:67620708 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 366: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); an α-helix

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.Leu366= Likely benign ★ same residue
CTCF p.Arg368His Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Glu187Ter 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-leu366phe (accessed [today's date]).

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