Is CTCF p.Arg371Cys (c.1111C>T) pathogenic?

CTCF p.Arg371Cys (c.1111C>T) is classified Uncertain significance in CTCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.9929); Absent from gnomAD v4.1; Associated with CTCF-related neurodevelopmental disorder.

What condition is associated with CTCF p.Arg371Cys (c.1111C>T)?

CTCF p.Arg371Cys (c.1111C>T) is associated with CTCF-related neurodevelopmental disorder (ClinVar).

How common is CTCF p.Arg371Cys (c.1111C>T) in the general population?

CTCF p.Arg371Cys (c.1111C>T) is absent from gnomAD v4.1 (gnomAD).

How is CTCF-related neurodevelopmental disorder inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CTCF p.Arg371Cys (c.1111C>T)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

CTCF p.Arg371Cys

c.1111C>T · rs2142847270 · VCV1805062

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,581,964)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTCF-related neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic
REVEL	0.544	indeterminate
SaProt	LLR -12.61	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 10 kb · p 3.4e-38 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,581,964). 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.Arg371Cys
Coding: c.1111C>T
MANE Select: NM_006565
dbSNP: rs2142847270
Type: single nucleotide variant
Location: chr16:67620721 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 371: 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 neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CTCF-related neurodevelopmental disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Childhood, Infancy, Neonatal

Similar variants

CTCF c.782-1G>A Pathogenic/Likely pathogenic ★★ same condition
CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same condition
CTCF c.782-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTCF c.782-2A>T Pathogenic ★★ same condition
CTCF p.Arg283His Likely pathogenic ★★ ⚠ same condition
CTCF p.Arg342Cys Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg342His Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Arg368Cys Pathogenic ★★ 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-arg371cys (accessed [today's date]).

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