BLK p.Pro223=
c.669G>A · rs775121719 · VCV2658406
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.54 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.02 · SpliceAI calls loss · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -3.9, phastCons 0.88 |
| Overall | ||
| CADD | 17.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,904 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00387%
Overall
0.00471%
76/1,614,030 alleles · ultra-rare
exomes 65/1,461,880 · genomes 11/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,363 |
| European (non-Finnish) | 0.00534% | 18,731 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| South Asian | 0.0022% | 45,541 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
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
- BLK
- Protein
- p.Pro223=
- Coding
- c.669G>A
- MANE Select
- NM_001715
- dbSNP
- rs775121719
- Type
- single nucleotide variant
- Location
- chr8:11555381 (GRCh38)
- Gene constraint
- LOEUF 1.295 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
Similar variants
- BLK p.Pro223Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- BLK p.Arg131Gln Uncertain significance ★★ ⚠ same type
- BLK p.Arg180His Uncertain significance ★★ ⚠ same type
- BLK p.Arg238Trp Uncertain significance ★★ ⚠ same type
- BLK p.Arg295Trp Uncertain significance ★★ same type
- BLK p.Arg298Gln Uncertain significance ★★ ⚠ same type
- BLK p.Arg466His Uncertain significance ★★ ⚠ same type
- BLK p.Asp68Val 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/blk-p-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown