ClinGen expert panel — Coagulation Factor Deficiency VCEP
Benign for hemophilia A. Applied ACMG criteria (verbatim):
BP4 BA1
Curation rationale (ClinGen, verbatim)
The c.3864A>C (p.Ser1288=) variant is reported at an MAF of 0.3377 (6437/19059 alleles) in the South Asian population in gnomAD v2.1.,1 with 3958 hemizygotes and 424 homozygotes, meeting BA1 criteria of MAF > 0.000333. The synonymous variant is predicted to have no impact on splicing based on SpliceAI score of 0.0, meeting BP4. 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.
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 1.9 | GERP 0.29, phastCons 1 |
| Overall | ||
| CADD | 3.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 34% | 3 |
| Admixed American | 23.8% | 4 |
| Middle Eastern | 22.8% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 17.6% | 6 |
| Remaining individualsnot grpmax-eligible | 13% | 8 |
| East Asian | 12.1% | 8 |
| Amishnot grpmax-eligible | 11.8% | 9 |
| European (non-Finnish) | 8.45% | 12 |
| African / African-American | 6.62% | 15 |
| Finnishnot grpmax-eligible | 5.98% | 17 |
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.Ser1288=
- Coding
- c.3864A>C
- MANE Select
- NM_000132
- dbSNP
- rs1800292
- Type
- single nucleotide variant
- Location
- chrX:154929926 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 1288
- the 'b' region
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-ser1288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown