CIC p.Arg140Gln
c.419G>A · rs529183042 · VCV1335346
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.816%, 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 -2.8 | GERP -2.1 |
| Overall | ||
| CADD | 0.076 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.816%
Middle Eastern · 13/1,594 alleles
Filtering AF
0.482%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.383%
Overall
0.0243%
97/398,940 alleles · rare
exomes 70/246,592 · genomes 27/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.816% | 123 |
| Admixed American | 0.0352% | 2,843 |
| Remaining individualsnot grpmax-eligible | 0.0324% | 3,083 |
| European (non-Finnish) | 0.0292% | 3,429 |
| Finnishnot grpmax-eligible | 0.00636% | 15,729 |
| African / African-American | 0.0041% | 24,383 |
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.Arg140Gln
- Coding
- c.419G>A
- MANE Select
- NM_001386298
- dbSNP
- rs529183042
- Type
- single nucleotide variant
- Location
- chr19:42272202 (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-arg140gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown