AP2A2 p.Pro671=
c.2013C>T · VCV4641457
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0428%, 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 -11 | GERP -3 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0428%
South Asian · 36/84,030 alleles
Filtering AF
0.0318%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0279%
Overall
0.00279%
43/1,539,776 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0428% | 2,334 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,924 |
| European (non-Finnish) | 0.000523% | 191,196 |
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
- AP2A2
- Protein
- p.Pro671=
- Coding
- c.2013C>T
- MANE Select
- NM_012305
- Type
- single nucleotide variant
- Location
- chr11:1000488 (GRCh38)
- Gene constraint
- LOEUF 0.437 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.30
- Residue 671
- the 'disordered' region
Similar variants
- AP2A2 p.Ala136Ser Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala136Thr Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala168Thr Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala274Pro Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala304Val Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala375Thr Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala3Val Uncertain significance ★ ⚠ same type
- AP2A2 p.Ala435Val 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/ap2a2-p-pro671 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown