BLOC1S3 p.Ala135Pro
c.403G>C · rs777289165 · VCV1493431
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8758 | likely pathogenic · top 4% in BLOC1S3 |
|---|---|---|
| REVEL | 0.312 | indeterminate |
| SaProt | LLR -12.00 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 605 bp · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 27.8 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0765% | 1,306 |
| Remaining individualsnot grpmax-eligible | 0.0071% | 14,086 |
| European (non-Finnish)grpmax | 0.000718% | 139,197 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Ala135Pro
- Coding
- c.403G>C
- MANE Select
- NM_212550
- dbSNP
- rs777289165
- Type
- single nucleotide variant
- Location
- chr19:45179699 (GRCh38)
- Gene constraint
- LOEUF 1.836 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.38
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-ala135pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown