CBLB p.Pro777=
c.2331A>G · rs56310324 · VCV3040464
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.26%, eas)
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 1.9 | GERP 0.63, phastCons 1 |
| Overall | ||
| CADD | 9.814 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.26%
East Asian · 1,016/44,866 alleles
Filtering AF
2.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.1%
Overall
0.0803%
1,296/1,614,096 alleles · low-frequency
exomes 1,133/1,461,804 · genomes 163/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 2.26% | 44 |
| Ashkenazi Jewishnot grpmax-eligible | 0.409% | 245 |
| Remaining individualsnot grpmax-eligible | 0.0928% | 1,078 |
| South Asian | 0.0472% | 2,118 |
| Middle Eastern | 0.033% | 3,031 |
| European (non-Finnish) | 0.00458% | 21,851 |
| Admixed American | 0.00167% | 60,020 |
| African / African-American | 0.00133% | 75,052 |
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.Pro777=
- Coding
- c.2331A>G
- MANE Select
- NM_170662
- dbSNP
- rs56310324
- Type
- single nucleotide variant
- Location
- chr3:105681576 (GRCh38)
- Gene constraint
- LOEUF 0.406 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.88 · 36 PDB
- Residue 777
- the 'disordered' region; a UniProt-annotated variant site (in admio3; likely pathogenic)
Similar variants
- CBLB p.Arg670Gln Benign/Likely benign ★★ same type
- CBLB p.Pro387= Benign ★★ same type
- CBLB p.Pro689= Benign/Likely benign ★★ same type
- CBLB p.Ser622Thr Benign/Likely benign ★★ same type
- CBLB c.2569+1609A>C Uncertain significance ★ same type
- CBLB p.Ala176Pro Uncertain significance ★ ⚠ same type
- CBLB p.Ala2Glu Uncertain significance ★ ⚠ same type
- CBLB p.Ala592Ser 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/cblb-p-pro777 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown