F2 p.Pro326=
c.978G>A · rs142949009 · VCV304814
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
2
thrombophilia due to thrombin defect
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -0.57, phastCons 0.61 |
| Overall | ||
| CADD | 7.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00886%
143/1,614,162 alleles · ultra-rare
exomes 135/1,461,816 · genomes 8/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| South Asian | 0.022% | 4,554 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| European (non-Finnish) | 0.00907% | 11,028 |
| Admixed American | 0.00333% | 30,018 |
| African / African-American | 0.00133% | 75,064 |
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.Pro326=
- Coding
- c.978G>A
- MANE Select
- NM_000506
- dbSNP
- rs142949009
- Type
- single nucleotide variant
- Location
- chr11:46726601 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 480 PDB
- Residue 326
- a turn
Similar variants
- F2 p.Pro326Arg 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-pro326 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown