AP2M1 p.Ser347=
c.1041C>T · rs770699298 · VCV1360206
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, sas)
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 -0.97 | GERP -3.7, phastCons 0.003 |
| Overall | ||
| CADD | 9.812 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
South Asian · 17/91,064 alleles
Filtering AF
0.0118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00976%
Overall
0.00143%
23/1,613,976 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0187% | 5,357 |
| East Asian | 0.00223% | 44,896 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,914 |
| European (non-Finnish) | 0.000254% | 393,340 |
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.Ser347=
- Coding
- c.1041C>T
- MANE Select
- NM_004068
- dbSNP
- rs770699298
- Type
- single nucleotide variant
- Location
- chr3:184182228 (GRCh38)
- Gene constraint
- LOEUF 0.182 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.44 · 3 PDB
- Residue 347
- the mhd domain; a turn
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-ser347 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown