ANGPT2 p.Ser166=
c.498G>C · rs139251288 · VCV735520
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.232%, 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 -0.17 | GERP -4, phastCons 0.007 |
| Overall | ||
| CADD | 1.247 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.232%
African / African-American · 174/74,964 alleles
Filtering AF
0.204%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.193%
Overall
0.0121%
196/1,613,794 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.232% | 431 |
| Middle Eastern | 0.0331% | 3,021 |
| Admixed American | 0.015% | 6,666 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,944 |
| East Asian | 0.00223% | 44,852 |
| European (non-Finnish) | 8.48e-05% | 1,179,896 |
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
- ANGPT2
- Protein
- p.Ser166=
- Coding
- c.498G>C
- MANE Select
- NM_001118887
- dbSNP
- rs139251288
- Type
- single nucleotide variant
- Location
- chr8:6527623 (GRCh38)
- Gene constraint
- LOEUF 0.606 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 84.15 · 7 PDB
Similar variants
- ANGPT2 p.Ile227Thr Uncertain significance ★★ ⚠ same type
- MCPH1 p.Leu730Gln Uncertain significance ★★ same type
- ANGPT2 c.566+9A>C Benign ★★ same type
- ANGPT2 p.Ala310Val Benign ★★ same type
- ANGPT2 p.Asp269His Benign/Likely benign ★★ same type
- ANGPT2 p.Leu402= Benign ★★ same type
- ANGPT2 p.Lys32= Benign ★★ same type
- ANGPT2 p.Thr154= 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/angpt2-p-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown