CIC p.Ala2233=
c.6699G>A · rs139872750 · VCV723051
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0769%, sas)
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 -2.9 | GERP -3.4 |
| Overall | ||
| CADD | 6.666 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0769%
South Asian · 70/91,042 alleles
Filtering AF
0.0624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0571%
Overall
0.0474%
764/1,612,818 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0769% | 1,301 |
| European (non-Finnish) | 0.0562% | 1,779 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,974 |
| Admixed American | 0.00666% | 15,006 |
| African / African-American | 0.00533% | 18,769 |
| East Asian | 0.00223% | 44,890 |
| Finnishnot grpmax-eligible | 0.00159% | 62,986 |
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.Ala2233=
- Coding
- c.6699G>A
- MANE Select
- NM_005984 · reported on NM_001386298
- dbSNP
- rs139872750
- Type
- single nucleotide variant
- Location
- chr19:42293768 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Similar variants
- CIC c.3179+1G>A Likely pathogenic ★★ same type
- CIC c.3179+1G>T Pathogenic ★★ same type
- CIC c.5903-2A>G Likely pathogenic ★★ same type
- CIC p.Asn1136Ser Likely pathogenic ★★ same type
- CIC p.Gln1134Ter Pathogenic ★★ same type
- CIC p.Gln1799Ter Likely pathogenic ★★ same type
- SLC25A1 c.821+1G>A Pathogenic ★★ same type
- SLC25A1 p.Ala274Val Pathogenic/Likely pathogenic ★★ 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/cic-p-ala2233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown