BLK p.Ile193=
c.579C>T · VCV3388788
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0248%, 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 0.045 | GERP -1.2 |
| Overall | ||
| CADD | 8.385 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0248%
European (non-Finnish) · 293/1,179,986 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0216%
Overall
0.0186%
300/1,613,968 alleles · ultra-rare
exomes 290/1,461,708 · genomes 10/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0248% | 4,027 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| African / African-American | 0.00267% | 37,516 |
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.Ile193=
- Coding
- c.579C>T
- MANE Select
- NM_001715
- Type
- single nucleotide variant
- Location
- chr8:11554849 (GRCh38)
- Gene constraint
- LOEUF 1.295 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 193
- the sh2 domain
Similar variants
- 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
- BLK p.Gln226Pro 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-ile193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown