CIC p.Ser2006=
c.6018T>C · rs142078348 · VCV735963
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.04%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -0.25 |
| Overall | ||
| CADD | 2.516 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.04%
South Asian · 950/91,086 alleles
Filtering AF
0.988%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.966%
Overall
0.119%
1,918/1,613,814 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.04% | 96 |
| Middle Eastern | 0.528% | 189 |
| Remaining individualsnot grpmax-eligible | 0.174% | 573 |
| Ashkenazi Jewishnot grpmax-eligible | 0.128% | 779 |
| Admixed American | 0.0666% | 1,500 |
| European (non-Finnish) | 0.0618% | 1,619 |
| African / African-American | 0.02% | 5,002 |
| Finnishnot grpmax-eligible | 0.0047% | 21,263 |
| East Asian | 0.00446% | 22,439 |
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.Ser2006=
- Coding
- c.6018T>C
- MANE Select
- NM_005984 · reported on NM_001386298
- dbSNP
- rs142078348
- Type
- single nucleotide variant
- Location
- chr19:42292681 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Similar variants
- CIC p.Ser2006Cys Uncertain significance ★ ⚠ same residue
- 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
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-ser2006 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown