CIC p.Ser1643=
c.4929G>A · rs770999487 · VCV754943
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00568%, nfe)
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 -4.6 | GERP -2.6 |
| Overall | ||
| CADD | 0.511 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00568%
European (non-Finnish) · 67/1,180,016 alleles
Filtering AF
0.00453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00459%
74/1,613,630 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00568% | 17,612 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| East Asian | 0.00446% | 22,445 |
| African / African-American | 0.00133% | 74,928 |
| South Asian | 0.0011% | 91,090 |
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.Ser1643=
- Coding
- c.4929G>A
- MANE Select
- NM_005984 · reported on NM_001386298
- dbSNP
- rs770999487
- Type
- single nucleotide variant
- Location
- chr19:42290970 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Similar variants
- CIC p.Ser1643Leu Conflicting classifications of pathogenicity ★ ⚠ 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-ser1643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown