ClinGen expert panel — Coagulation Factor Deficiency VCEP
Benign for hemophilia A. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
The c.1086G>A (p.Ala362=) variant is reported at an MAF of 0.03761 (713/18957 alleles) in the African/African-American population in gnomAD v2.1.1 with 201 hemizygotes, meeting BA1 criteria of MAF > 0.000333. SpliceAI predicts no impact on splicing with scores of 0, and the nucleotide is not conserved based on agreement between PhyloP (-2.25) and PhastCons (0) scores meeting BP4 and BP7. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8/F9: BA1, BP4, BP7.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 -5.5 | GERP -3 |
| Overall | ||
| CADD | 1.671 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.77% | 26 |
| Remaining individualsnot grpmax-eligible | 0.261% | 384 |
| Admixed American | 0.234% | 427 |
| Middle Eastern | 0.0689% | 1,451 |
| South Asian | 0.0247% | 4,053 |
| East Asian | 0.0148% | 6,748 |
| European (non-Finnish) | 0.00335% | 29,822 |
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
- F8
- Protein
- p.Ala362=
- Coding
- c.1086G>A
- MANE Select
- NM_000132
- dbSNP
- rs1800289
- Type
- single nucleotide variant
- Location
- chrX:154966611 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
Disease context
hemophilia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hemophilia A (Orphanet):
- Inheritance
- X-linked recessive
- Onset
- Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- F8 c.6429+2T>A Pathogenic ★★★ same condition
- F8 p.Ala111Thr Likely pathogenic ★★★ same condition
- F8 p.Ala2220Pro Pathogenic ★★★ same condition
- F8 p.Ala415Asp Likely pathogenic ★★★ same condition
- F8 p.Ala415Val Pathogenic ★★★ ⚠ same condition
- F8 p.Arg1768His Pathogenic ★★★ ⚠ same condition
- F8 p.Arg1800His Pathogenic ★★★ same condition
- F8 p.Arg2016Trp Pathogenic ★★★ 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/f8-p-ala362 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown