AP2M1 p.Asp417=
c.1251T>C · rs1488958639 · VCV2086860
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 -0.81 | GERP -0.41, phastCons 0.017 |
| Overall | ||
| CADD | 8.023 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,906 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000248%
4/1,614,012 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,969 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- AP2M1
- Protein
- p.Asp417=
- Coding
- c.1251T>C
- MANE Select
- NM_004068
- dbSNP
- rs1488958639
- Type
- single nucleotide variant
- Location
- chr3:184183559 (GRCh38)
- Gene constraint
- LOEUF 0.182 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.44 · 3 PDB
- Residue 417
- the mhd domain; an α-helix
Similar variants
- AP2M1 p.Arg170Trp Pathogenic/Likely pathogenic ★★ same type
- AP2M1 p.Ala28Thr Uncertain significance ★★ ⚠ same type
- AP2M1 p.Arg169His Uncertain significance ★★ ⚠ same type
- AP2M1 p.Arg199Gln Uncertain significance ★★ ⚠ same type
- AP2M1 p.Arg40Trp Uncertain significance ★★ ⚠ same type
- AP2M1 p.Arg44His Uncertain significance ★★ ⚠ same type
- AP2M1 p.Cys246Arg Uncertain significance ★★ ⚠ same type
- AP2M1 p.Cys86Tyr 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/ap2m1-p-asp417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown