Is CIC p.Arg1130Cys (c.3388C>T) pathogenic?

CIC p.Arg1130Cys (c.3388C>T) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). AlphaMissense: likely pathogenic (0.9909); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CIC p.Arg1130Cys (c.3388C>T)?

CIC p.Arg1130Cys (c.3388C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CIC p.Arg1130Cys (c.3388C>T) in the general population?

CIC p.Arg1130Cys (c.3388C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIC p.Arg1130Cys (c.3388C>T)?

AlphaMissense predicts likely pathogenic (score 0.9909) — an in-silico prediction, not a clinical call.

CIC p.Arg1130Cys

c.3388C>T · VCV3492891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9909	likely pathogenic
REVEL	0.365	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R221C vs ClinVar R1130C) — verify the residue.

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: CIC
Protein: p.Arg1130Cys
Coding: c.3388C>T
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42287623 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC c.2795-2056C>T Uncertain significance ★★ ⚠ same condition
CIC p.Ala1228Val Uncertain significance ★★ ⚠ same condition
CIC p.Ala1445Gly Uncertain significance ★★ ⚠ same condition
CIC p.Ala1750Val Uncertain significance ★★ ⚠ same condition
CIC p.Ala1975Gly Uncertain significance ★★ ⚠ same condition
CIC p.Ala2463Thr Uncertain significance ★★ ⚠ same condition
CIC p.Arg1205Trp Uncertain significance ★★ ⚠ same condition
CIC p.Arg1481Gln Uncertain significance ★★ ⚠ same condition

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/cic-p-arg1130cys (accessed [today's date]).

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