F2 p.Thr165=
c.495G>A · rs144857547 · VCV756801
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0626%, sas)
Conditions
2
thrombophilia due to thrombin defect
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -3.8 |
| Overall | ||
| CADD | 0.075 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0626%
South Asian · 57/91,070 alleles
Filtering AF
0.0496%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0449%
Overall
0.0348%
561/1,614,090 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0626% | 1,598 |
| European (non-Finnish) | 0.0406% | 2,463 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Admixed American | 0.005% | 20,004 |
| Finnishnot grpmax-eligible | 0.00469% | 21,339 |
| African / African-American | 0.00267% | 37,521 |
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.Thr165=
- Coding
- c.495G>A
- MANE Select
- NM_000506
- dbSNP
- rs144857547
- Type
- single nucleotide variant
- Location
- chr11:46723454 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 480 PDB
- Residue 165
- a disulfide bond; a UniProt-annotated variant site (confirmed at protein level); the kringle 1 domain
Similar variants
- F2 p.Thr165Met Benign/Likely benign ★★ 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-thr165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown