CIB2 p.Glu64=
c.192G>A · rs145415848 · VCV259970
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.412%, mid)
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 3.6 | GERP -0.93, phastCons 1 |
| Overall | ||
| CADD | 11.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.412%
Middle Eastern · 25/6,062 alleles
Filtering AF
0.287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.245%
Overall
0.011%
178/1,613,958 alleles · rare
exomes 161/1,461,652 · genomes 17/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.412% | 242 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0946% | 1,057 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,404 |
| Admixed American | 0.0333% | 3,001 |
| African / African-American | 0.0133% | 7,504 |
| European (non-Finnish) | 0.00551% | 18,152 |
| South Asian | 0.00329% | 30,359 |
| East Asian | 0.00223% | 44,884 |
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.Glu64=
- Coding
- c.192G>A
- MANE Select
- NM_006383
- dbSNP
- rs145415848
- Type
- single nucleotide variant
- Location
- chr15:78111171 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 64
- a UniProt-annotated variant site (in dfnb48); a UniProt-annotated variant site (in dfnb48; decreases interaction with tmc1 and tmc2); a turn
Similar variants
- CIB2 p.Glu64Asp 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-glu64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown