Is CTCF p.Cys327Arg (c.979T>C) pathogenic?

CTCF p.Cys327Arg (c.979T>C) is classified Pathogenic in CTCF (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-07). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is CTCF p.Cys327Arg (c.979T>C) in the general population?

CTCF p.Cys327Arg (c.979T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Cys327Arg (c.979T>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CTCF p.Cys327Arg

c.979T>C · rs2052136913 · VCV973091

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 6% in CTCF
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -16.52	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	29.6	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.Cys327Arg
Coding: c.979T>C
MANE Select: NM_006565
dbSNP: rs2052136913
Type: single nucleotide variant
Location: chr16:67616771 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 327: a UniProt-annotated variant site (found in an endometrial carcinoma sample; uncertain significance); a β-strand

Full CTCF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTCF p.Cys327Ser Likely pathogenic ★ same residue
CTCF p.Cys327= Likely benign ★ same residue
CTCF c.782-1G>A Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-1G>C Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-2A>G Pathogenic/Likely pathogenic ★★ same type
CTCF c.782-2A>T Pathogenic ★★ same type
CTCF p.Arg283His Likely pathogenic ★★ same type
CTCF p.Arg342Cys 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-cys327arg (accessed [today's date]).

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