Is CLIC2 p.Phe117= (c.351T>C) pathogenic?

CLIC2 p.Phe117= (c.351T>C) is classified Likely benign in CLIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Very rare (popmax 0.00168%, nfe).

How common is CLIC2 p.Phe117= (c.351T>C) in the general population?

CLIC2 p.Phe117= (c.351T>C) is very rare (popmax 0.00168%, nfe) (gnomAD).

CLIC2 p.Phe117=

c.351T>C · rs781981574 · VCV3067786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, nfe)

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 2.4	GERP 0.63, phastCons 1
Overall
CADD	8.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% European (non-Finnish) · 15/894,041 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000799%

Overall 0.00124% 15/1,208,904 alleles · very rare

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.Phe117=
Coding: c.351T>C
MANE Select: NM_001289
dbSNP: rs781981574
Type: single nucleotide variant
Location: chrX:155280011 (GRCh38)
Structure: AlphaFold pLDDT 93.28 · 3 PDB
Residue 117: the gst c-terminal domain; an α-helix; the 'c-terminal' region

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

Similar variants

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
CLIC2 p.Arg214His Conflicting classifications of pathogenicity ★ ⚠ same type
CLIC2 p.Arg222Cys 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-phe117 (accessed [today's date]).

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