APP p.Ile716Val
c.2145_2146delinsTG · rs2146237965 · VCV1457308
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Conditions
1
Alzheimer disease
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 289 kb · p 2e-07 · regional, not allelic |
Population frequency
dbSNP / gnomAD
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- APP
- Protein
- p.Ile716Val
- Coding
- c.2145_2146delinsTG
- MANE Select
- NM_000484
- dbSNP
- rs2146237965
- Type
- Indel
- Location
- chr21:25891787 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.11 · 263 PDB
- Residue 716
- a UniProt-annotated variant site (in ad1); a turn; the 'interaction with psen1' region
Similar variants
- APP p.Ile716Phe Pathogenic ★★ ⚠ same residue
- APP p.Ile716= Benign ★★ same residue
- APP p.Ile716Thr Pathogenic ★ ⚠ same residue
- APP p.Ile716Met Likely pathogenic ★ ⚠ same residue
- APP p.Asp360_Lys363delinsGln Uncertain significance ★ same condition
- APP p.Ala713Thr Likely pathogenic ★★ ⚠ same condition
- APP p.Asp694Asn Pathogenic ★★ ⚠ same condition
- APP p.Glu693Gln Pathogenic ★★ ⚠ same condition
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/app-p-ile716val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown