Is CTCF p.Pro195Ala (c.583C>G) pathogenic?

CTCF p.Pro195Ala (c.583C>G) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-02). AlphaMissense: likely benign (0.1554); Absent from gnomAD v4.1.

How common is CTCF p.Pro195Ala (c.583C>G) in the general population?

CTCF p.Pro195Ala (c.583C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCF p.Pro195Ala (c.583C>G)?

AlphaMissense predicts likely benign (score 0.1554) — an in-silico prediction, not a clinical call.

CTCF p.Pro195Ala

c.583C>G · rs2543449162 · VCV2440602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1554 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1554	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -7.49	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 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 162 bp · p 0.19 · regional, not allelic
Overall
CADD	26.1	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.Pro195Ala
Coding: c.583C>G
MANE Select: NM_006565
dbSNP: rs2543449162
Type: single nucleotide variant
Location: chr16:67611415 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 195: the 'disordered' region; 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

Similar variants

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
CTCF p.Arg342His Pathogenic/Likely pathogenic ★★ same type
CTCF p.Arg368Cys 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-pro195ala (accessed [today's date]).

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