APPL1 p.Thr12=
c.36G>C · rs79282761 · VCV1183160
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 -1.2 | GERP -3.5 |
| Overall | ||
| CADD | 9.879 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 6.6% | 15 |
| Remaining individualsnot grpmax-eligible | 0.434% | 231 |
| European (non-Finnish)grpmax | 0.364% | 275 |
| Ashkenazi Jewishnot grpmax-eligible | 0.32% | 312 |
| Middle Eastern | 0.221% | 452 |
| South Asian | 0.13% | 770 |
| Admixed American | 0.0178% | 5,610 |
| African / African-American | 0.0176% | 5,695 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Thr12=
- Coding
- c.36G>C
- MANE Select
- NM_012096
- dbSNP
- rs79282761
- Type
- single nucleotide variant
- Location
- chr3:57227919 (GRCh38)
- Gene constraint
- LOEUF 0.524 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 81.44 · 8 PDB
- Residue 12
- the bar domain; a turn; the 'required for rab5a binding' region
Disease context
maturity-onset diabetes of the young type 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MODY (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- APPL1 p.Arg275Gln Uncertain significance ★★ ⚠ same condition
- APPL1 p.Arg478Cys Uncertain significance ★★ ⚠ same condition
- APPL1 p.Arg72Cys Uncertain significance ★★ ⚠ same condition
- APPL1 p.Thr565Met Uncertain significance ★★ ⚠ same condition
- APPL1 p.Tyr36Cys Uncertain significance ★★ ⚠ same condition
- APPL1 p.Asp334Glu Benign/Likely benign ★★ same condition
- APPL1 p.Glu67Gly Benign/Likely benign ★★ ⚠ same condition
- APPL1 p.Ile642Met Likely benign ★★ 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/appl1-p-thr12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown