CIC p.Pro1427=
c.4281G>A · rs142884630 · VCV3049080
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
1
CIC-related disorder
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 -2.6 | GERP -3.1 |
| Overall | ||
| CADD | 1.958 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,002 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00335%
54/1,613,876 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,001 |
| European (non-Finnish) | 0.00398% | 25,105 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| African / African-American | 0.00134% | 74,852 |
| South Asian | 0.0011% | 91,090 |
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.Pro1427=
- Coding
- c.4281G>A
- MANE Select
- NM_005984 · reported on NM_001386298
- dbSNP
- rs142884630
- Type
- single nucleotide variant
- Location
- chr19:42290322 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Disease context
CIC-related disorder
Similar variants
- CIC p.Pro1427Ser Likely benign ★ same residue
- CIC p.Asn1136Ser Likely pathogenic ★★ same condition
- SLC25A1 p.Ala274Val Pathogenic/Likely pathogenic ★★ same condition
- SLC25A1 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same condition
- CIC p.Arg2114Trp Uncertain significance ★★ ⚠ same condition
- CIC p.Arg800His Uncertain significance ★★ same condition
- CIC p.Gly17Val Uncertain significance ★★ same condition
- CIC p.Val989Ala 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-pro1427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown