BCL11A p.Pro35=
c.105G>A · VCV4955292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 | GERP -5.3 |
| Overall | ||
| CADD | 8.842 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00235%
38/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Finnishnot grpmax-eligible | 0.00312% | 32,012 |
| European (non-Finnish) | 0.00271% | 36,876 |
| South Asian | 0.0022% | 45,541 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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
- BCL11A
- Protein
- p.Pro35=
- Coding
- c.105G>A
- MANE Select
- NM_022893
- Type
- single nucleotide variant
- Location
- chr2:60546251 (GRCh38)
- Gene constraint
- LOEUF 0.125 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.09 · 17 PDB
- Residue 35
- the 'required for nuclear body formation and for sumo1 recruitment' region; the 'disordered' region
Similar variants
- BCL11A c.385+2T>C Pathogenic ★★ same type
- BCL11A c.488-1G>A Pathogenic/Likely pathogenic ★★ same type
- BCL11A p.Gln124Ter Pathogenic/Likely pathogenic ★★ same type
- BCL11A p.Glu473Ter Pathogenic/Likely pathogenic ★★ same type
- BCL11A p.Met1Val Pathogenic/Likely pathogenic ★★ same type
- BCL11A p.Arg713His Uncertain significance ★★ ⚠ same type
- BCL11A p.Cys48Arg Uncertain significance ★★ ⚠ same type
- BCL11A p.Gly610Ser 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/bcl11a-p-pro35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown