AP2A1 p.Ala365=
c.1095C>T · rs201278183 · VCV782059
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.66%, mid)
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 -20 | GERP -2.4 |
| Overall | ||
| CADD | 0.658 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.66%
Middle Eastern · 161/6,058 alleles
Filtering AF
2.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.19%
Overall
0.369%
5,947/1,611,686 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.66% | 38 |
| South Asian | 1.71% | 59 |
| Ashkenazi Jewishnot grpmax-eligible | 1.52% | 66 |
| Remaining individualsnot grpmax-eligible | 0.641% | 156 |
| Admixed American | 0.495% | 202 |
| European (non-Finnish) | 0.253% | 395 |
| African / African-American | 0.124% | 806 |
| East Asian | 0.00669% | 14,937 |
| Finnishnot grpmax-eligible | 0.00477% | 20,977 |
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
- AP2A1
- Protein
- p.Ala365=
- Coding
- c.1095C>T
- MANE Select
- NM_130787
- dbSNP
- rs201278183
- Type
- single nucleotide variant
- Location
- chr19:49799456 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.78
Similar variants
- AP2A1 c.2115-388C>T Benign ★★ same type
- AP2A1 c.2114+403C>T Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-363G>A Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-371C>A Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-372G>A Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-383T>C Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-383T>G Uncertain significance ★ ⚠ same type
- AP2A1 c.2115-384A>G 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/ap2a1-p-ala365 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown