CIC p.Pro189Thr
c.565C>A · rs543498277 · VCV1694922
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.32%, mid)
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 1.1, phastCons 1 |
| Overall | ||
| CADD | 19.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.32%
Middle Eastern · 21/1,588 alleles
Filtering AF
0.886%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.745%
Overall
0.164%
654/398,550 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.32% | 76 |
| South Asian | 0.864% | 116 |
| Ashkenazi Jewishnot grpmax-eligible | 0.362% | 276 |
| Admixed American | 0.303% | 330 |
| Remaining individualsnot grpmax-eligible | 0.189% | 528 |
| European (non-Finnish) | 0.168% | 595 |
| Finnishnot grpmax-eligible | 0.0604% | 1,655 |
| African / African-American | 0.0328% | 3,047 |
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.Pro189Thr
- Coding
- c.565C>A
- MANE Select
- NM_005984 · reported on NM_001386298
- dbSNP
- rs543498277
- Type
- single nucleotide variant
- Location
- chr19:42272348 (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-pro189thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown