Is CIC p.Arg2405Cys (c.7213C>T) pathogenic?

CIC p.Arg2405Cys (c.7213C>T) is classified Likely benign in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). AlphaMissense: likely pathogenic (0.7519); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CIC p.Arg2405Cys (c.7213C>T)?

CIC p.Arg2405Cys (c.7213C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CIC p.Arg2405Cys (c.7213C>T) in the general population?

CIC p.Arg2405Cys (c.7213C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CIC p.Arg2405Cys (c.7213C>T)?

AlphaMissense predicts likely pathogenic (score 0.7519) — an in-silico prediction, not a clinical call.

CIC p.Arg2405Cys

c.7213C>T · VCV3833413

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7519	likely pathogenic
REVEL	0.603	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	25.6	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 R1496C vs ClinVar R2405C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,038 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00162% 26/1,601,390 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,519
European (non-Finnish)	0.00186%	53,634
Admixed American	0.00167%	60,018
South Asian	0.0011%	91,084

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: CIC
Protein: p.Arg2405Cys
Coding: c.7213C>T
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42294850 (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 p.Arg2405Leu Uncertain significance ★ ⚠ same residue
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

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-arg2405cys (accessed [today's date]).

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