Is CLIC1 p.Pro6Arg (c.17C>G) pathogenic?

CLIC1 p.Pro6Arg (c.17C>G) is classified Uncertain significance in CLIC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.3297); Absent from gnomAD v4.1.

How common is CLIC1 p.Pro6Arg (c.17C>G) in the general population?

CLIC1 p.Pro6Arg (c.17C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLIC1 p.Pro6Arg (c.17C>G)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

CLIC1 p.Pro6Arg

c.17C>G · VCV4003634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -14.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,455 bp · p 0.00014 · regional, not allelic
Overall
CADD	24.1	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: CLIC1
Protein: p.Pro6Arg
Coding: c.17C>G
MANE Select: NM_001288
Type: single nucleotide variant
Location: chr6:31736284 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.34 · 18 PDB
Residue 6: an α-helix; the 'required for insertion into the membrane' region

Full CLIC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIC1 p.Ala157Asp Uncertain significance ★ ⚠ same type
CLIC1 p.Arg204Pro Uncertain significance ★ ⚠ same type
CLIC1 p.Arg92Ser Uncertain significance ★ ⚠ same type
CLIC1 p.Glu234Lys Uncertain significance ★ ⚠ same type
CLIC1 p.Glu4Gly Uncertain significance ★ ⚠ same type
CLIC1 p.Glu9Lys Uncertain significance ★ ⚠ same type
CLIC1 p.Gly196Arg Uncertain significance ★ ⚠ same type
CLIC1 p.Gly61Val 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/clic1-p-pro6arg (accessed [today's date]).

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