CIB2 p.Ile123=
c.369C>T · rs758763586 · VCV1922499
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 16.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
South Asian · 15/91,088 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00124%
20/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0165% | 6,073 |
| European (non-Finnish) | 0.000424% | 236,006 |
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.Ile123=
- Coding
- c.369C>T
- MANE Select
- NM_006383
- dbSNP
- rs758763586
- Type
- single nucleotide variant
- Location
- chr15:78105912 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 123
- a UniProt-annotated variant site (in dfnb48); the ef-hand 2 domain; a UniProt-annotated variant site (in dfnb48; uncertain significance); a UniProt-annotated variant site (in dfnb48; stimulates the ability to decrease atp-induced calcium release; decreases interaction with tmc1 and tmc2); a β-strand
Similar variants
- CIB2 p.Ile123Thr 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
- CIB2 p.Arg134Gln 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-ile123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown