F2 p.Thr488=
c.1464G>A · rs146742525 · VCV304816
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 -8.8 | GERP -3.8 |
| Overall | ||
| CADD | 0.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.123% | 812 |
| European (non-Finnish)grpmax | 0.104% | 962 |
| Finnishnot grpmax-eligible | 0.0642% | 1,558 |
| African / African-American | 0.028% | 3,574 |
| Admixed American | 0.0133% | 7,502 |
| South Asian | 0.00329% | 30,354 |
| East Asian | 0.00223% | 44,886 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- F2
- Protein
- p.Thr488=
- Coding
- c.1464G>A
- MANE Select
- NM_000506
- dbSNP
- rs146742525
- Type
- single nucleotide variant
- Location
- chr11:46728829 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 480 PDB
- Residue 488
- the peptidase s1 domain; an α-helix
Disease context
congenital prothrombin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: thrombophilia due to thrombin defect
For Congenital factor II deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- <1 / 1 000 000 (Europe)
Similar variants
- F2 p.Thr488Met Uncertain significance ★★ ⚠ same residue
- F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
- F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
- F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same condition
- F2 p.Arg596Gln Pathogenic ★★ ⚠ same condition
- F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same condition
- F2 c.559+5G>A Uncertain significance ★★ same condition
- F2 p.Ala17Ser Uncertain significance ★★ ⚠ 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/f2-p-thr488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown