Is CTCFL p.Val652Met (c.1954G>A) pathogenic?

CTCFL p.Val652Met (c.1954G>A) is classified Benign in CTCFL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-18). AlphaMissense: likely benign (0.0998); Low-frequency (popmax 4.88%, afr).

How common is CTCFL p.Val652Met (c.1954G>A) in the general population?

CTCFL p.Val652Met (c.1954G>A) is low-frequency (popmax 4.88%, afr) (gnomAD).

What do computational predictors say about CTCFL p.Val652Met (c.1954G>A)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

CTCFL p.Val652Met

c.1954G>A · rs28472888 · VCV775652

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.88%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.16	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 -5.9	GERP -2.2
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.87 · regional, not allelic
Overall
CADD	0.002	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 4.88% African / African-American · 3,664/75,020 alleles

Filtering AF 4.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.7%

Overall 0.256% 4,140/1,614,096 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.88%	20
Remaining individualsnot grpmax-eligible	0.339%	295
Admixed American	0.31%	323
Middle Eastern	0.116%	864
South Asian	0.00988%	10,120
European (non-Finnish)	0.00525%	19,032

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: CTCFL
Protein: p.Val652Met
Coding: c.1954G>A
MANE Select: NM_001386993
dbSNP: rs28472888
Type: single nucleotide variant
Location: chr20:57498588 (GRCh38)
Gene constraint: LOEUF 0.669 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.75

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

Similar variants

CTCFL p.Ser172= Benign ★★ same type
CTCFL p.Ala155Ser Uncertain significance ★ ⚠ same type
CTCFL p.Ala155Thr Uncertain significance ★ ⚠ same type
CTCFL p.Ala253Thr Uncertain significance ★ ⚠ same type
CTCFL p.Ala321Thr Uncertain significance ★ ⚠ same type
CTCFL p.Ala434Thr Uncertain significance ★ ⚠ same type
CTCFL p.Ala438Thr Uncertain significance ★ ⚠ same type
CTCFL p.Ala494Val Uncertain significance ★ ⚠ 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/ctcfl-p-val652met (accessed [today's date]).

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