CBLB p.Gln540=
c.1620A>G · rs115014051 · VCV3050124
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.348%, nfe)
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 1.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 8.171 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.348%
European (non-Finnish) · 4,099/1,177,966 alleles
Filtering AF
0.339%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.335%
Overall
0.269%
4,323/1,605,556 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.348% | 287 |
| Remaining individualsnot grpmax-eligible | 0.141% | 708 |
| Finnishnot grpmax-eligible | 0.14% | 715 |
| African / African-American | 0.0633% | 1,579 |
| Admixed American | 0.00511% | 19,551 |
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.Gln540=
- Coding
- c.1620A>G
- MANE Select
- NM_170662
- dbSNP
- rs115014051
- Type
- single nucleotide variant
- Location
- chr3:105702433 (GRCh38)
- Gene constraint
- LOEUF 0.406 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.88 · 36 PDB
- Residue 540
- a UniProt-annotated variant site (in admio3; likely pathogenic); the 'disordered' region
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-gln540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown