BLOC1S3 p.Ala75=
c.225C>T · rs1435023179 · VCV2977948
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0224%, 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 -2.5 | GERP -2.9 |
| Overall | ||
| CADD | 8.649 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0224%
Middle Eastern · 1/4,460 alleles
Filtering AF
0.000838%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.000328%
5/1,523,160 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0224% | 4,460 |
| East Asian | 0.00506% | 19,781 |
| South Asian | 0.00121% | 82,728 |
| European (non-Finnish) | 8.75e-05% | 1,142,610 |
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
- BLOC1S3
- Protein
- p.Ala75=
- Coding
- c.225C>T
- MANE Select
- NM_212550
- dbSNP
- rs1435023179
- Type
- single nucleotide variant
- Location
- chr19:45179521 (GRCh38)
- Gene constraint
- LOEUF 1.836 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.38
- Residue 75
- the 'disordered' region
Similar variants
- BLOC1S3 p.Ala103Val Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Ala169Ser Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Ala60Thr Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Arg106Pro Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Arg112Gln Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Arg112Leu Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Asp197His Uncertain significance ★★ ⚠ same type
- BLOC1S3 p.Gln150Arg 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/bloc1s3-p-ala75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown