Is CTCF p.Pro643Ser (c.1927C>T) pathogenic?

CTCF p.Pro643Ser (c.1927C>T) is classified Benign/Likely benign in CTCF (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0876); Rare (popmax 0.604%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTCF p.Pro643Ser (c.1927C>T)?

CTCF p.Pro643Ser (c.1927C>T) is associated with Inborn genetic diseases, CTCF-related neurodevelopmental disorder (ClinVar).

How common is CTCF p.Pro643Ser (c.1927C>T) in the general population?

CTCF p.Pro643Ser (c.1927C>T) is rare (popmax 0.604%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Pro643Ser (c.1927C>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

CTCF p.Pro643Ser

c.1927C>T · rs145727304 · VCV210800

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.604%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -8.82	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, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 8,396 bp · p 0.23 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.604% European (non-Finnish) · 7,107/1,176,036 alleles

Filtering AF 0.593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.588%

Overall 0.468% 7,521/1,605,712 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.604%	165
Remaining individualsnot grpmax-eligible	0.413%	242
African / African-American	0.0951%	1,052
Admixed American	0.0916%	1,092
Finnishnot grpmax-eligible	0.0407%	2,460
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,754
South Asian	0.00449%	22,293

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTCF
Protein: p.Pro643Ser
Coding: c.1927C>T
MANE Select: NM_006565
dbSNP: rs145727304
Type: single nucleotide variant
Location: chr16:67636779 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 643: 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

Disease context

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

Also linked: CTCF-related neurodevelopmental disorder

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-pro643ser (accessed [today's date]).

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