FCSK p.Ala558=
c.1674G>A · rs771305367 · VCV1682377
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.146%, amr)
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 -5.8 | GERP -3.1 |
| Overall | ||
| CADD | 0.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.146%
Admixed American · 74/50,848 alleles
Filtering AF
0.119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.109%
Overall
0.0466%
714/1,532,930 alleles · rare
exomes 612/1,380,756 · genomes 102/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.146% | 687 |
| Finnishnot grpmax-eligible | 0.113% | 885 |
| Remaining individualsnot grpmax-eligible | 0.0554% | 1,806 |
| European (non-Finnish) | 0.0474% | 2,111 |
| Ashkenazi Jewishnot grpmax-eligible | 0.021% | 4,761 |
| African / African-American | 0.00686% | 14,572 |
| South Asian | 0.00119% | 83,822 |
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
- FCSK
- Protein
- p.Ala558=
- Coding
- c.1674G>A
- MANE Select
- NM_145059
- dbSNP
- rs771305367
- Type
- single nucleotide variant
- Location
- chr16:70473250 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- FCSK p.Ala558Val 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-ala558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown