CBLB p.Leu447=
c.1341A>C · rs2305036 · VCV3057240
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 30.1%, amr) — too common for a highly-penetrant pathogenic allele
Conditions
1
CBLB-related disorder
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 -1.5 | GERP -4.3 |
| Overall | ||
| CADD | 1.913 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
30.1%
Admixed American · 18,052/59,962 alleles
Filtering AF
29.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 29.6%
Overall
21.9%
353,245/1,613,332 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 30.1% | 3 |
| Finnishnot grpmax-eligible | 27.4% | 4 |
| Amishnot grpmax-eligible | 24.1% | 4 |
| East Asian | 23.1% | 4 |
| European (non-Finnish) | 22.1% | 5 |
| Remaining individualsnot grpmax-eligible | 21.4% | 5 |
| African / African-American | 19.3% | 5 |
| Middle Eastern | 14.7% | 7 |
| South Asian | 14.6% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 14.1% | 7 |
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
- CBLB
- Protein
- p.Leu447=
- Coding
- c.1341A>C
- MANE Select
- NM_170662
- dbSNP
- rs2305036
- Type
- single nucleotide variant
- Location
- chr3:105720113 (GRCh38)
- Gene constraint
- LOEUF 0.406 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.88 · 36 PDB
Disease context
CBLB-related disorder
Similar variants
- CBLB p.Ala621= Benign same condition
- CBLB p.Arg570= Likely benign same condition
- CBLB p.Asn466Asp Benign same condition
- CBLB p.Asn883Asp Benign same condition
- CBLB p.Asp351= Benign same condition
- CBLB p.Asp424= Benign same condition
- CBLB p.Lys275= Benign same condition
- CBLB p.Pro280= Benign same condition
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/cblb-p-leu447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown