Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.95%, afr) — too common for a highly-penetrant pathogenic allele
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 -1.2 | |
| Overall | ||
| CADD | 1.246 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.95%
African / African-American · 4,460/75,012 alleles
Filtering AF
5.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.74%
Overall
0.32%
5,161/1,613,926 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.95% | 17 |
| Remaining individualsnot grpmax-eligible | 0.49% | 204 |
| Admixed American | 0.455% | 220 |
| Middle Eastern | 0.28% | 357 |
| European (non-Finnish) | 0.00839% | 11,919 |
| South Asian | 0.00659% | 15,175 |
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
- PTGS2
- Protein
- p.His403=
- Coding
- c.1209T>C
- MANE Select
- NM_000963
- dbSNP
- rs5279
- Type
- single nucleotide variant
- Location
- chr1:186675946 (GRCh38)
- Gene constraint
- LOEUF 0.33 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 93.37 · 7 PDB
- Residue 403
- an α-helix
Similar variants
- PTGS2 p.Arg585= Benign ★★ same type
- PTGS2 p.Asp300= Benign ★★ same type
- PTGS2 p.Ala436Ser Uncertain significance ★ ⚠ same type
- PTGS2 p.Ala475Thr Uncertain significance ★ ⚠ same type
- PTGS2 p.Ala529Ser Uncertain significance ★ ⚠ same type
- PTGS2 p.Ala529Val Uncertain significance ★ ⚠ same type
- PTGS2 p.Ala581Gly Uncertain significance ★ ⚠ same type
- PTGS2 p.Ala581Thr 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/ptgs2-p-his403 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown