F12 p.Leu367=
c.1101G>C · rs1328103815 · VCV2656120
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 0.64 | GERP 0.97, phastCons 1 |
| Overall | ||
| CADD | 10.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,868 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000749%
12/1,602,368 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00669% | 14,956 |
| Admixed American | 0.00167% | 59,956 |
| European (non-Finnish) | 0.000678% | 147,462 |
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
- F12
- Protein
- p.Leu367=
- Coding
- c.1101G>C
- MANE Select
- NM_000505
- dbSNP
- rs1328103815
- Type
- single nucleotide variant
- Location
- chr5:177404008 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 367
- a disulfide bond
Similar variants
- F12 p.Glu193Ter Pathogenic/Likely pathogenic ★★ same type
- F12 p.Thr328Lys Pathogenic ★★ ⚠ same type
- F12 c.57+4A>G Uncertain significance ★★ same type
- F12 p.Ala452Thr Uncertain significance ★★ ⚠ same type
- F12 p.Arg55Trp Uncertain significance ★★ ⚠ same type
- F12 p.Asp283= Uncertain significance ★★ same type
- F12 p.Glu288Lys Uncertain significance ★★ same type
- F12 p.Gly360Val 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/f12-p-leu367 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown