CIB2 p.Leu41=
c.123C>T · rs780117405 · VCV1109104
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 -4.4 | GERP -2.8 |
| Overall | ||
| CADD | 5.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,926 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00155%
25/1,614,062 alleles · very rare
exomes 22/1,461,842 · genomes 3/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,463 |
| European (non-Finnish) | 0.00186% | 53,638 |
| South Asian | 0.0011% | 91,092 |
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.Leu41=
- Coding
- c.123C>T
- MANE Select
- NM_006383
- dbSNP
- rs780117405
- Type
- single nucleotide variant
- Location
- chr15:78111240 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 41
- a UniProt-annotated variant site (in dfnb48); a turn
Similar variants
- CIB2 p.Leu41Phe 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-leu41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown