Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.6%, 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 -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.138 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.6%
African / African-American · 3,448/74,918 alleles
Filtering AF
4.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.42%
Overall
0.241%
3,891/1,613,816 alleles · low-frequency
exomes 1,876/1,461,826 · genomes 2,015/151,990 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.6% | 22 |
| Remaining individualsnot grpmax-eligible | 0.294% | 340 |
| Admixed American | 0.207% | 484 |
| Middle Eastern | 0.198% | 505 |
| South Asian | 0.034% | 2,938 |
| European (non-Finnish) | 0.0078% | 12,826 |
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
- SERPINE1
- Protein
- p.Asp216=
- Coding
- c.648C>T
- MANE Select
- NM_000602
- dbSNP
- rs2227670
- Type
- single nucleotide variant
- Location
- chr7:101132017 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.03 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.68 · 29 PDB
- Residue 216
- a β-strand
Similar variants
- SERPINE1 c.*617T>A Uncertain significance ★★ same type
- SERPINE1 p.Asp240Gly Uncertain significance ★★ ⚠ same type
- SERPINE1 p.Gly196Ser Uncertain significance ★★ ⚠ same type
- SERPINE1 p.Leu175Pro Uncertain significance ★★ ⚠ same type
- SERPINE1 p.Phe157Leu Uncertain significance ★★ ⚠ same type
- SERPINE1 p.Pro372Ala Uncertain significance ★★ ⚠ same type
- SERPINE1 c.1088-106A>G Benign ★★ same type
- SERPINE1 c.1088-9C>T Benign/Likely benign ★★ 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/serpine1-p-asp216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown