F8A1 p.Ala328=
c.984T>C · VCV4873296
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.932%, 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 -1.5 | GERP -2.6 |
| Overall | ||
| CADD | 7.707 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.932%
Admixed American · 320/34,346 alleles
Filtering AF
0.848%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.815%
Overall
0.0777%
770/991,445 alleles · rare
exomes 714/926,004 · genomes 56/65,441 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.932% | 107 |
| African / African-American | 0.176% | 569 |
| Remaining individualsnot grpmax-eligible | 0.137% | 731 |
| Finnishnot grpmax-eligible | 0.0838% | 1,194 |
| Middle Eastern | 0.0745% | 1,342 |
| South Asian | 0.0421% | 2,376 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0401% | 2,494 |
| European (non-Finnish) | 0.0388% | 2,576 |
| East Asian | 0.0273% | 3,666 |
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
- F8A1
- Protein
- p.Ala328=
- Coding
- c.984T>C
- MANE Select
- NM_012151
- Type
- single nucleotide variant
- Location
- chrX:154887358 (GRCh38)
- Structure
- AlphaFold pLDDT 78.88 · 10 PDB
- Residue 328
- an α-helix
Similar variants
- F8A1 p.Gly11Cys Uncertain significance ★ same type
- F8A1 p.Gly14Ala Uncertain significance ★ same type
- F8A1 p.Leu279Val Uncertain significance ★ same type
- F8A1 p.Leu360Arg Uncertain significance ★ same type
- F8A1 p.Leu8Arg Uncertain significance ★ same type
- F8A1 p.Pro15Arg Uncertain significance ★ same type
- F8A1 p.Thr329Ile Uncertain significance ★ same type
- F8A1 p.Val342Leu 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/f8a1-p-ala328 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown