Is CTCFL p.Ser172= (c.516C>T) pathogenic?

CTCFL p.Ser172= (c.516C>T) is classified Benign in CTCFL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-18). Common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele.

CTCFL p.Ser172=

Q: How common is CTCFL p.Ser172= (c.516C>T) in the general population?

CTCFL p.Ser172= (c.516C>T) is common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.516C>T · rs11907063 · VCV781569

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.63	donor gain · deltas
Pangolin	Δ0.59	gain · loss 0.36 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.3	GERP 1.3, phastCons 0.58
Overall
CADD	17.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.82% African / African-American · 4,368/75,034 alleles

Filtering AF 5.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.62%

Overall 0.468% 7,557/1,613,484 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.82%	17
Amishnot grpmax-eligible	3.29%	30
South Asian	2.22%	45
Remaining individualsnot grpmax-eligible	0.642%	156
Admixed American	0.623%	160
Middle Eastern	0.363%	276
Finnishnot grpmax-eligible	0.178%	561
East Asian	0.103%	976
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
European (non-Finnish)	0.0125%	7,973

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.Ser172=
Coding: c.516C>T
MANE Select: NM_001386993
dbSNP: rs11907063
Type: single nucleotide variant
Location: chr20:57523690 (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.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
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-ser172 (accessed [today's date]).

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