CIB2 p.Thr131=
c.393G>A · rs34057735 · VCV226516
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 15.8%, sas) — too common for a highly-penetrant pathogenic allele
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 -13 | GERP -2.8 |
| Overall | ||
| CADD | 0.962 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15.8%
South Asian · 14,408/91,080 alleles
Filtering AF
15.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 15.5%
Overall
4.49%
72,486/1,614,138 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 15.8% | 6 |
| Middle Eastern | 9.17% | 11 |
| African / African-American | 8.34% | 12 |
| Ashkenazi Jewishnot grpmax-eligible | 5.71% | 18 |
| Remaining individualsnot grpmax-eligible | 5.07% | 20 |
| European (non-Finnish) | 3.69% | 27 |
| Admixed American | 3.24% | 31 |
| Finnishnot grpmax-eligible | 1.32% | 76 |
| Amishnot grpmax-eligible | 0.439% | 228 |
| East Asian | 0.049% | 2,040 |
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.Thr131=
- Coding
- c.393G>A
- MANE Select
- NM_006383
- dbSNP
- rs34057735
- Type
- single nucleotide variant
- Location
- chr15:78105888 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 131
- a UniProt-annotated variant site (in dfnb48); the ef-hand 2 domain; a UniProt-annotated variant site (in dfnb48; uncertain significance); an α-helix
Similar variants
- CIB2 p.Thr131Met Uncertain significance ★ ⚠ 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-thr131 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown