Is CTCF p.Cys353Gly (c.1057T>G) pathogenic?

CTCF p.Cys353Gly (c.1057T>G) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with CTCF p.Cys353Gly (c.1057T>G)?

CTCF p.Cys353Gly (c.1057T>G) is associated with intellectual disability (ClinVar).

How common is CTCF p.Cys353Gly (c.1057T>G) in the general population?

CTCF p.Cys353Gly (c.1057T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Cys353Gly (c.1057T>G)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

CTCF p.Cys353Gly

c.1057T>G · rs2052138115 · VCV981361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 10 kb · p 3.4e-38 · regional, not allelic
Overall
CADD	26.8	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

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.Cys353Gly
Coding: c.1057T>G
MANE Select: NM_006565
dbSNP: rs2052138115
Type: single nucleotide variant
Location: chr16:67616849 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 353: 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

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTCF p.Cys353Arg Uncertain significance ★ ⚠ same residue
CTCF p.Arg567Trp Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Cys353fs Likely pathogenic ★ same residue
CTCF p.Gln94Ter Likely pathogenic ★ same condition
CTCF p.Asp46Asn Likely benign same condition
CTCF p.Lys206fs Pathogenic ★★ same condition
CTCF c.782-1G>A Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-1G>C Pathogenic/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-cys353gly (accessed [today's date]).

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