Is CTCFL p.Ser212Cys (c.634A>T) pathogenic?

CTCFL p.Ser212Cys (c.634A>T) is classified Uncertain significance in CTCFL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1195); Ultra-rare (popmax 0.0494%, afr).

How common is CTCFL p.Ser212Cys (c.634A>T) in the general population?

CTCFL p.Ser212Cys (c.634A>T) is ultra-rare (popmax 0.0494%, afr) (gnomAD).

What do computational predictors say about CTCFL p.Ser212Cys (c.634A>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

CTCFL p.Ser212Cys

c.634A>T · rs372695377 · VCV2250797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.52	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 0.97	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.09	unconstrained · MANE · 4,856 bp · p 0.1 · regional, not allelic
Overall
CADD	12.61	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 0.0494% African / African-American · 37/74,922 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00248% 40/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0494%	2,025
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ser212Cys
Coding: c.634A>T
MANE Select: NM_001386993
dbSNP: rs372695377
Type: single nucleotide variant
Location: chr20:57523188 (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.Ser212Arg Likely benign ★ same residue
CTCFL p.Ser172= Benign ★★ same type
CTCFL p.Val652Met 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

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-ser212cys (accessed [today's date]).

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