FCSK p.Ala107=
c.321T>C · rs17880268 · VCV1682346
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 25.5%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.22 | GERP -3.4, phastCons 0.97 |
| Overall | ||
| CADD | 7.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.5%
African / African-American · 19,109/74,912 alleles
Filtering AF
25.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25.1%
Overall
1.34%
21,550/1,613,766 alleles · common
exomes 10,519/1,461,642 · genomes 11,031/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 25.5% | 4 |
| Remaining individualsnot grpmax-eligible | 1.76% | 57 |
| Admixed American | 1.59% | 63 |
| Middle Eastern | 0.792% | 126 |
| South Asian | 0.0494% | 2,024 |
| European (non-Finnish) | 0.0248% | 4,027 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
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
- FCSK
- Protein
- p.Ala107=
- Coding
- c.321T>C
- MANE Select
- NM_145059
- dbSNP
- rs17880268
- Type
- single nucleotide variant
- Location
- chr16:70466167 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- FCSK p.Ala107Asp Uncertain significance ★ ⚠ same residue
- FCSK c.412-2A>G Likely pathogenic ★★ same type
- FCSK c.485-2A>G Uncertain significance ★★ same type
- FCSK p.Ala297Val Uncertain significance ★★ ⚠ same type
- FCSK p.Ala348Ser Uncertain significance ★★ ⚠ same type
- FCSK p.Ala481Thr Uncertain significance ★★ ⚠ same type
- FCSK p.Ala488Thr Uncertain significance ★★ same type
- FCSK p.Ala518Val 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/fcsk-p-ala107 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown