APPL1 p.Pro402=
c.1206A>G · rs34128429 · VCV782428
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.68%, afr)
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 -1.9 | GERP -3.7 |
| Overall | ||
| CADD | 4.563 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.68%
African / African-American · 2,009/75,022 alleles
Filtering AF
2.58%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.54%
Overall
0.153%
2,468/1,614,132 alleles · low-frequency
exomes 1,232/1,461,878 · genomes 1,236/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.68% | 37 |
| Admixed American | 0.24% | 417 |
| Middle Eastern | 0.231% | 433 |
| Remaining individualsnot grpmax-eligible | 0.219% | 456 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0642% | 1,558 |
| European (non-Finnish) | 0.0119% | 8,369 |
| South Asian | 0.00439% | 22,772 |
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
- APPL1
- Protein
- p.Pro402=
- Coding
- c.1206A>G
- MANE Select
- NM_012096
- dbSNP
- rs34128429
- Type
- single nucleotide variant
- Location
- chr3:57257010 (GRCh38)
- Gene constraint
- LOEUF 0.524 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 81.44 · 8 PDB
- Residue 402
- the 'required for rab5a binding' region; the 'disordered' region
Similar variants
- APPL1 c.1658+6T>G Uncertain significance ★★ same type
- APPL1 p.Arg275Gln Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg407Ser Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg412Trp Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg478Cys Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg526His Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg633His Uncertain significance ★★ ⚠ same type
- APPL1 p.Arg72Cys 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/appl1-p-pro402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown