Is CTCF p.Leu40Phe (c.120A>T) pathogenic?

CTCF p.Leu40Phe (c.120A>T) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.0973); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Leu40Phe (c.120A>T)?

CTCF p.Leu40Phe (c.120A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTCF p.Leu40Phe (c.120A>T) in the general population?

CTCF p.Leu40Phe (c.120A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Leu40Phe (c.120A>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

CTCF p.Leu40Phe

c.120A>T · rs2543446871 · VCV3078561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -5.6, phastCons 0.99
Regional constraint	o/e 0.76	unconstrained · MANE · 465 bp · p 0.00078 · regional, not allelic
Overall
CADD	13.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Leu40Phe
Coding: c.120A>T
MANE Select: NM_006565
dbSNP: rs2543446871
Type: single nucleotide variant
Location: chr16:67610952 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 40: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTCF p.Leu40Val Uncertain significance ★ ⚠ same residue
CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg368Cys Pathogenic ★★ same condition
CTCF p.Pro378Leu Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg277Gln Uncertain significance ★★ ⚠ same condition
CTCF p.Cys299Arg Uncertain significance ★★ ⚠ same condition
CTCF p.Gly597Arg Uncertain significance ★★ ⚠ same condition
CTCF p.Gly657Arg 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-leu40phe (accessed [today's date]).

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