CIC p.Pro1072=
c.3216T>C · rs375676767 · VCV3047632
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, sas)
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 0.36 | GERP 1.2, phastCons 0.99 |
| Overall | ||
| CADD | 8.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
South Asian · 32/91,086 alleles
Filtering AF
0.0256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00217%
35/1,614,082 alleles · ultra-rare
exomes 35/1,461,850 · genomes 0/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0351% | 2,846 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.000169% | 590,009 |
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.Pro1072=
- Coding
- c.3216T>C
- MANE Select
- NM_001386298
- dbSNP
- rs375676767
- Type
- single nucleotide variant
- Location
- chr19:42287356 (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-pro1072 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown