Is CTAG2 p.Ile23Thr (c.68T>C) pathogenic?

CTAG2 p.Ile23Thr (c.68T>C) is classified Uncertain significance in CTAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: ambiguous (0.357); Ultra-rare (popmax 0.0193%, nfe).

How common is CTAG2 p.Ile23Thr (c.68T>C) in the general population?

CTAG2 p.Ile23Thr (c.68T>C) is ultra-rare (popmax 0.0193%, nfe) (gnomAD).

What do computational predictors say about CTAG2 p.Ile23Thr (c.68T>C)?

AlphaMissense predicts ambiguous (score 0.357) — an in-silico prediction, not a clinical call.

CTAG2 p.Ile23Thr

c.68T>C · rs1454281517 · VCV2332235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.357 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.357	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -4.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -1.8
Regional constraint	o/e 0.97	unconstrained · MANE · 1,329 bp · p 0.74 · regional, not allelic
Overall
CADD	0.031	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 0.0193% European (non-Finnish) · 165/855,267 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0154% 173/1,125,449 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0193%	5,183
Remaining individualsnot grpmax-eligible	0.0112%	8,909
African / African-American	0.00394%	25,359
South Asian	0.00205%	48,863

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: CTAG2
Protein: p.Ile23Thr
Coding: c.68T>C
MANE Select: NM_172377
dbSNP: rs1454281517
Type: single nucleotide variant
Location: chrX:154653448 (GRCh38)
Structure: AlphaFold pLDDT 47.90
Residue 23: the 'disordered' region

Full CTAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAG2 c.405-28T>C Likely benign ★★ same type
CTAG2 c.405-93G>C Benign ★★ same type
CTAG2 p.Met94Val Benign ★★ same type
CTAG2 p.Pro99Ala Benign ★★ same type
CTAG2 c.404+107C>A Uncertain significance ★ ⚠ same type
CTAG2 c.404+21G>C Uncertain significance ★ ⚠ same type
CTAG2 c.404+35C>T Uncertain significance ★ ⚠ same type
CTAG2 c.404+42G>A 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/ctag2-p-ile23thr (accessed [today's date]).

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