Is CTCF p.Val50Met (c.148G>A) pathogenic?

CTCF p.Val50Met (c.148G>A) is classified Uncertain significance in CTCF (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-01). AlphaMissense: likely benign (0.0992); Very rare (popmax 0.00513%, nfe).

How common is CTCF p.Val50Met (c.148G>A) in the general population?

CTCF p.Val50Met (c.148G>A) is very rare (popmax 0.00513%, nfe) (gnomAD).

What do computational predictors say about CTCF p.Val50Met (c.148G>A)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

CTCF p.Val50Met

c.148G>A · rs137861966 · VCV1711410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00513%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 465 bp · p 0.00078 · regional, not allelic
Overall
CADD	24.6	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 0.00513% European (non-Finnish) · 60/1,169,350 alleles

Filtering AF 0.00406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00365%

Overall 0.00387% 62/1,601,090 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00513%	19,489
Remaining individualsnot grpmax-eligible	0.00162%	61,796
African / African-American	0.00134%	74,674

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.Val50Met
Coding: c.148G>A
MANE Select: NM_006565
dbSNP: rs137861966
Type: single nucleotide variant
Location: chr16:67610980 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.45 · 21 PDB
Residue 50: 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 p.Val50= Likely benign ★ same residue
CTCF p.Val50fs Pathogenic ★ 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-val50met (accessed [today's date]).

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