CIB2 p.Phe122=
c.366C>T · rs374836619 · VCV1119392
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.06%, 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 3.9 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 14.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.06%
African / African-American · 45/75,052 alleles
Filtering AF
0.046%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0411%
Overall
0.00335%
54/1,614,138 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.06% | 1,668 |
| Admixed American | 0.005% | 20,012 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| European (non-Finnish) | 0.000254% | 393,334 |
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.Phe122=
- Coding
- c.366C>T
- MANE Select
- NM_006383
- dbSNP
- rs374836619
- Type
- single nucleotide variant
- Location
- chr15:78105915 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.71 · 1 PDB
- Residue 122
- a UniProt-annotated variant site (in dfnb48); the ef-hand 2 domain; a UniProt-annotated variant site (in dfnb48; uncertain significance); a β-strand
Similar variants
- 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
- CIB2 p.Arg134Trp 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-phe122 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown