Is CTCFL p.Ala321Thr (c.961G>A) pathogenic?

CTCFL p.Ala321Thr (c.961G>A) is classified Uncertain significance in CTCFL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.5652); Absent from gnomAD v4.1.

How common is CTCFL p.Ala321Thr (c.961G>A) in the general population?

CTCFL p.Ala321Thr (c.961G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTCFL p.Ala321Thr (c.961G>A)?

AlphaMissense predicts likely pathogenic (score 0.5652) — an in-silico prediction, not a clinical call.

CTCFL p.Ala321Thr

c.961G>A · rs995538553 · VCV2251625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5652 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5652	likely pathogenic
REVEL	0.292	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTCFL
Protein: p.Ala321Thr
Coding: c.961G>A
MANE Select: NM_001386993
dbSNP: rs995538553
Type: single nucleotide variant
Location: chr20:57518856 (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.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.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-ala321thr (accessed [today's date]).

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