F2 p.Tyr136=
c.408C>T · VCV4535648
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 · C>G here scores Δ0.31 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 10.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,980 alleles
Overall
0.000124%
2/1,613,980 alleles · very rare
exomes 0/1,461,852 · genomes 2/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,980 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Tyr136=
- Coding
- c.408C>T
- MANE Select
- NM_000506
- Type
- single nucleotide variant
- Location
- chr11:46723271 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 480 PDB
- Residue 136
- the kringle 1 domain; a β-strand
Similar variants
- F2 p.Arg314His Likely pathogenic ★★ ⚠ same type
- F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same type
- F2 p.Arg500Gln Pathogenic ★★ ⚠ same type
- F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same type
- F2 p.Arg596Gln Pathogenic ★★ ⚠ same type
- F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same type
- F2 c.559+5G>A Uncertain significance ★★ same type
- F2 p.Ala17Ser 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/f2-p-tyr136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown