CIB2 p.Cys99=
c.297C>T · rs370965183 · VCV957351
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00769%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.31 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -2.8 |
| Overall | ||
| CADD | 14.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,026 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00291%
47/1,612,352 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,004 |
| African / African-American | 0.00539% | 18,538 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,817 |
| European (non-Finnish) | 0.00254% | 39,323 |
| East Asian | 0.00223% | 44,816 |
| Admixed American | 0.00167% | 59,772 |
| Finnishnot grpmax-eligible | 0.00157% | 63,856 |
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
- CIB2
- Protein
- p.Cys99=
- Coding
- c.297C>T
- MANE Select
- NM_006383
- dbSNP
- rs370965183
- Type
- single nucleotide variant
- Location
- chr15:78109284 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 99
- the ef-hand 1 domain; a UniProt-annotated variant site (in dfnb48); a UniProt-annotated variant site (in dfnb48; inhibits the ability to decrease atp-induced calcium release; decreases interaction with tmc1 and tmc2)
Similar variants
- CIB2 p.Cys99Arg Uncertain significance ★ ⚠ same residue
- CIB2 p.Cys99Trp Pathogenic/Likely pathogenic same residue
- CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
- CIB2 p.Arg33Ter Pathogenic ★★ same type
- CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- CIB2 c.198+3A>G Uncertain significance ★★ same type
- CIB2 p.Ala108Thr Uncertain significance ★★ ⚠ same type
- CIB2 p.Ala76Val Uncertain significance ★★ ⚠ 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/cib2-p-cys99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown