Is CLIC2 p.Thr152= (c.456C>T) pathogenic?

CLIC2 p.Thr152= (c.456C>T) is classified Likely benign in CLIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). Very rare (popmax 0.00219%, amr).

How common is CLIC2 p.Thr152= (c.456C>T) in the general population?

CLIC2 p.Thr152= (c.456C>T) is very rare (popmax 0.00219%, amr) (gnomAD).

CLIC2 p.Thr152=

c.456C>T · VCV4953797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -3, phastCons 0.002
Overall
CADD	3.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,766 alleles

Overall 0.000166% 2/1,207,931 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,766
European (non-Finnish)	0.000112%	893,296

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: CLIC2
Protein: p.Thr152=
Coding: c.456C>T
MANE Select: NM_001289
Type: single nucleotide variant
Location: chrX:155279275 (GRCh38)
Structure: AlphaFold pLDDT 93.28 · 3 PDB
Residue 152: the gst c-terminal domain; the 'c-terminal' region; the 'foot loop' region

Full CLIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIC2 p.Thr152Ala Uncertain significance ★ ⚠ same residue
CLIC2 p.Thr152Asn Uncertain significance ★ ⚠ same residue
CLIC2 c.57+10C>T Benign/Likely benign ★★ same type
CLIC2 c.*19= Benign ★★ same type
CLIC2 p.Pro160Ala Benign/Likely benign ★★ same type
CLIC2 c.582+6T>C Uncertain significance ★ same type
CLIC2 p.Ala131Thr Uncertain significance ★ ⚠ same type
CLIC2 p.Arg170Gly 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/clic2-p-thr152 (accessed [today's date]).

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