Is CLIC3 p.Phe115Tyr (c.344T>A) pathogenic?

CLIC3 p.Phe115Tyr (c.344T>A) is classified Uncertain significance in CLIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1437); Absent from gnomAD v4.1.

How common is CLIC3 p.Phe115Tyr (c.344T>A) in the general population?

CLIC3 p.Phe115Tyr (c.344T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLIC3 p.Phe115Tyr (c.344T>A)?

AlphaMissense predicts likely benign (score 0.1437) — an in-silico prediction, not a clinical call.

CLIC3 p.Phe115Tyr

c.344T>A · VCV4003639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1437	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -2.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,859 bp · p 0.23 · regional, not allelic
Overall
CADD	16.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: CLIC3
Protein: p.Phe115Tyr
Coding: c.344T>A
MANE Select: NM_004669
Type: single nucleotide variant
Location: chr9:136995218 (GRCh38)
Gene constraint: LOEUF 1.903 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 2 PDB
Residue 115: an α-helix; the gst c-terminal domain

Full CLIC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIC3 p.Ala151Val Uncertain significance ★ ⚠ same type
CLIC3 p.Ala188Thr Uncertain significance ★ ⚠ same type
CLIC3 p.Ala209Thr Uncertain significance ★ ⚠ same type
CLIC3 p.Ala2Val Uncertain significance ★ ⚠ same type
CLIC3 p.Arg191Cys Uncertain significance ★ ⚠ same type
CLIC3 p.Arg200His Uncertain significance ★ ⚠ same type
CLIC3 p.Arg204Ser Uncertain significance ★ ⚠ same type
CLIC3 p.Arg27Gln 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/clic3-p-phe115tyr (accessed [today's date]).

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