AP3D1 p.Thr893Met
c.2678C>T · rs568784323 · VCV2154749
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0039%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.035 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.2 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 8,543 bp · p 0.28 · regional, not allelic |
| Overall | ||
| CADD | 3.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0039%
European (non-Finnish) · 41/1,051,116 alleles
Filtering AF
0.0029%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00261%
Overall
0.00291%
41/1,410,310 alleles · very rare
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
- AP3D1
- Protein
- p.Thr893Met
- Coding
- c.2678C>T
- MANE Select
- NM_001261826
- dbSNP
- rs568784323
- Type
- single nucleotide variant
- Location
- chr19:2113337 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.45 · 6 PDB
- Residue 893
- the 'disordered' region
Similar variants
- AP3D1 p.Thr893= Uncertain significance ★ same residue
- AP3D1 p.Thr893Ala Uncertain significance ★ same residue
- AP3D1 c.2001+6C>T Uncertain significance ★★ same type
- AP3D1 c.2601+6G>T Uncertain significance ★★ same type
- AP3D1 c.856+3G>A Uncertain significance ★★ same type
- AP3D1 p.Ala1076Val Uncertain significance ★★ ⚠ same type
- AP3D1 p.Ala1093Val Uncertain significance ★★ ⚠ same type
- AP3D1 p.Ala1148Val 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/ap3d1-p-thr893met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown