F8 p.Val1866=
c.5598G>A · VCV3911600
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.11%, amr)
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 0.033 | GERP -2.5, phastCons 0.86 |
| Overall | ||
| CADD | 5.162 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.11%
Admixed American · 50/45,649 alleles
Filtering AF
0.0853%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0767%
Overall
0.0188%
226/1,204,246 alleles · rare
exomes 193/1,092,958 · genomes 33/111,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.11% | 913 |
| Middle Eastern | 0.0461% | 2,170 |
| Remaining individualsnot grpmax-eligible | 0.0232% | 4,314 |
| European (non-Finnish) | 0.0174% | 5,744 |
| Finnishnot grpmax-eligible | 0.00644% | 15,519 |
| South Asian | 0.0053% | 18,882 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00455% | 21,999 |
| African / African-American | 0.00176% | 56,916 |
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.Val1866=
- Coding
- c.5598G>A
- MANE Select
- NM_000132
- Type
- single nucleotide variant
- Location
- chrX:154904513 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 1866
- the f5/8 type a 3 domain; the plastocyanin-like 5 domain; an α-helix
Similar variants
- F8 c.6429+2T>A Pathogenic ★★★ same type
- F8 p.Ala111Thr Likely pathogenic ★★★ same type
- F8 p.Ala2220Pro Pathogenic ★★★ same type
- F8 p.Ala415Asp Likely pathogenic ★★★ same type
- F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
- F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
- F8 p.Arg1800His Pathogenic ★★★ same type
- F8 p.Arg2016Trp Pathogenic ★★★ 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/f8-p-val1866 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown