AP2B1 p.Leu199=
c.597G>A · rs141661445 · VCV773590
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.11%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | phastCons 1 |
| Overall | ||
| CADD | 13.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.11%
European (non-Finnish) · 13,144/1,179,996 alleles
Filtering AF
1.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.09%
Overall
0.901%
14,547/1,614,120 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.11% | 90 |
| Finnishnot grpmax-eligible | 0.739% | 135 |
| Remaining individualsnot grpmax-eligible | 0.666% | 150 |
| Admixed American | 0.52% | 192 |
| Middle Eastern | 0.247% | 404 |
| African / African-American | 0.195% | 514 |
| Ashkenazi Jewishnot grpmax-eligible | 0.132% | 759 |
| South Asian | 0.0022% | 45,539 |
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
- AP2B1
- Protein
- p.Leu199=
- Coding
- c.597G>A
- MANE Select
- NM_001030006
- dbSNP
- rs141661445
- Type
- single nucleotide variant
- Location
- chr17:35624468 (GRCh38)
- Gene constraint
- LOEUF 0.275 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.48 · 22 PDB
Similar variants
- AP2B1 p.Ala612Thr Uncertain significance ★ ⚠ same type
- AP2B1 p.Ala723Val Uncertain significance ★ ⚠ same type
- AP2B1 p.Ala77Gly Uncertain significance ★ ⚠ same type
- AP2B1 p.Arg746His Uncertain significance ★ ⚠ same type
- AP2B1 p.Asn152Ser Uncertain significance ★ ⚠ same type
- AP2B1 p.Asn179Asp Uncertain significance ★ ⚠ same type
- AP2B1 p.Asn195Ser Uncertain significance ★ ⚠ same type
- AP2B1 p.Asn579Ser 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/ap2b1-p-leu199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown