APPL1 c.415+96del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 85.7%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +96 | deep intronic (+96 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -2.8 |
| Non-coding constraint | Z 0.12 | 1 kb window · o/e 0.99 · regional · uncalibrated |
| Overall | ||
| CADD | 3.717 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
85.7%
East Asian · 31,521/36,766 alleles
Filtering AF
84.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 84.6%
Overall
39.3%
370,125/941,586 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 85.7% | 1 |
| Admixed American | 54.8% | 2 |
| Amishnot grpmax-eligible | 53.5% | 2 |
| Finnishnot grpmax-eligible | 48.5% | 2 |
| South Asian | 46.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 46.4% | 2 |
| Middle Eastern | 43.1% | 2 |
| Remaining individualsnot grpmax-eligible | 40% | 3 |
| European (non-Finnish) | 36.3% | 3 |
| African / African-American | 15% | 7 |
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
- Coding
- c.415+96del
- MANE Select
- NM_012096
- dbSNP
- rs11346575
- Type
- Deletion
- Location
- chr3:57242231 (GRCh38)
- Gene constraint
- LOEUF 0.524 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 81.44 · 8 PDB
Similar variants
- APPL1 p.Glu652fs Uncertain significance ★ same type
- APPL1 c.1842+321del Likely benign ★ same type
- APPL1 c.1894-294del Likely benign ★ same type
- APPL1 c.373+248_373+256del Likely benign ★ same type
- APPL1 c.622-16del Likely benign ★ 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-c-415-plus-96del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown