Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 49.9%, amr) — too common for a highly-penetrant pathogenic allele
Conditions
4
thrombophilia due to thrombin defect
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 -20 | GERP -3.4 |
| Overall | ||
| CADD | 0.059 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
49.9%
Admixed American · 28,674/57,454 alleles
Filtering AF
49.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 49.2%
Overall
33.4%
528,132/1,581,322 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 49.9% | 2 |
| South Asian | 40% | 2 |
| Middle Eastern | 36.7% | 3 |
| European (non-Finnish) | 33.3% | 3 |
| Remaining individualsnot grpmax-eligible | 32.8% | 3 |
| Finnishnot grpmax-eligible | 30.7% | 3 |
| East Asian | 29% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 24.8% | 4 |
| Amishnot grpmax-eligible | 24.2% | 4 |
| African / African-American | 21.5% | 5 |
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
- F5
- Protein
- p.Ser1268=
- Coding
- c.3804T>C
- MANE Select
- NM_000130
- dbSNP
- rs1800594
- Type
- single nucleotide variant
- Location
- chr1:169541286 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.57 · 23 PDB
- Residue 1268
- the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region
Similar variants
- F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1030Ter Pathogenic ★★ same condition
- F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Asp96His Pathogenic ★★ same condition
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/f5-p-ser1268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown