APP p.Gln104=
c.312G>A · rs370274393 · VCV2168134
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
Conditions
1
Alzheimer disease
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.294 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.22 | GERP -0.67, phastCons 0.97 |
| Overall | ||
| CADD | 9.639 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,932 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00031%
5/1,614,106 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
- APP
- Protein
- p.Gln104=
- Coding
- c.312G>A
- MANE Select
- NM_000484
- dbSNP
- rs370274393
- Type
- single nucleotide variant
- Location
- chr21:26089986 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.11 · 263 PDB
- Residue 104
- the e1 domain; a β-strand; the 'gfld subdomain' region; a binding site; a disulfide bond
Similar variants
- APP p.Ala713Thr Likely pathogenic ★★ ⚠ same condition
- APP p.Asp694Asn Pathogenic ★★ ⚠ same condition
- APP p.Glu693Gln Pathogenic ★★ ⚠ same condition
- APP p.Ile716Phe Pathogenic ★★ ⚠ same condition
- APP p.Thr714Ala Pathogenic ★★ ⚠ same condition
- APP p.Val715Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
- APP p.Val717Ile Pathogenic ★★ ⚠ same condition
- APP p.Val717Phe 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-gln104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown