AP3D1 p.Val1158=
c.3474T>C · rs772395600 · VCV1625143
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00874%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.96 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.19 | GERP -2, phastCons 0.41 |
| Overall | ||
| CADD | 3.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00874%
European (non-Finnish) · 101/1,155,734 alleles
Filtering AF
0.00731%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00682%
Overall
0.0069%
108/1,566,292 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00874% | 11,443 |
| Remaining individualsnot grpmax-eligible | 0.00659% | 15,178 |
| Admixed American | 0.00377% | 26,543 |
| African / African-American | 0.00136% | 73,516 |
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
- AP3D1
- Protein
- p.Val1158=
- Coding
- c.3474T>C
- MANE Select
- NM_001261826
- dbSNP
- rs772395600
- Type
- single nucleotide variant
- Location
- chr19:2108765 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.45 · 6 PDB
Similar variants
- AP3D1 p.Val1158Ile Likely benign ★★ same residue
- AP3D1 p.Val1158Leu 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-val1158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown