CIC p.Pro157=
c.471C>A · rs536081766 · VCV3050160
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.269%, afr)
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 -0.58 | GERP -1.4, phastCons 0.001 |
| Overall | ||
| CADD | 4.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.269%
African / African-American · 131/48,744 alleles
Filtering AF
0.231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.217%
Overall
0.0346%
138/398,616 alleles · rare
exomes 14/246,294 · genomes 124/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.269% | 372 |
| Remaining individualsnot grpmax-eligible | 0.0216% | 4,621 |
| Admixed American | 0.0088% | 11,368 |
| European (non-Finnish) | 0.000442% | 226,062 |
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.Pro157=
- Coding
- c.471C>A
- MANE Select
- NM_001386298
- dbSNP
- rs536081766
- Type
- single nucleotide variant
- Location
- chr19:42272254 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Disease context
CIC-related disorder
Similar variants
- 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
- CIC p.Arg800Cys Likely pathogenic ★ 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-pro157 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown