Is CTCF p.Val10Ala (c.29T>C) pathogenic?

CTCF p.Val10Ala (c.29T>C) is classified Uncertain significance in CTCF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely benign (0.1072); Very rare (popmax 0.000178%, nfe); Associated with CTCF-related disorder.

What condition is associated with CTCF p.Val10Ala (c.29T>C)?

CTCF p.Val10Ala (c.29T>C) is associated with CTCF-related disorder (ClinVar).

How common is CTCF p.Val10Ala (c.29T>C) in the general population?

CTCF p.Val10Ala (c.29T>C) is very rare (popmax 0.000178%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Val10Ala (c.29T>C)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

CTCF p.Val10Ala

c.29T>C · rs1434204599 · VCV2632030

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTCF-related disorder

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.70	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 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 465 bp · p 0.00078 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.000178% European (non-Finnish) · 2/1,124,264 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000133% 2/1,500,500 alleles · very rare

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.Val10Ala
Coding: c.29T>C
MANE Select: NM_006565
dbSNP: rs1434204599
Type: single nucleotide variant
Location: chr16:67610861 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB

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

Disease context

CTCF-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTCF p.Arg368His Pathogenic/Likely pathogenic ★★ same condition
CTCF p.Glu187Ter Likely pathogenic ★ same condition
CTCF p.Leu366Phe Likely pathogenic ★ same condition
CTCF p.Met329Val Likely pathogenic ★ same condition
CTCF p.Ala697Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
CTCF p.Cys472Arg Uncertain significance ★ ⚠ same condition
CTCF p.Ala669Thr Uncertain significance ⚠ same condition
CTCF p.Gly375Glu Uncertain significance ⚠ 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-val10ala (accessed [today's date]).

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