FCSK p.Ala348=
c.1044C>G · rs17880985 · VCV2052560
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.567%, nfe)
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 -0.31 | GERP -1.9, phastCons 0.12 |
| Overall | ||
| CADD | 5.947 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.567%
European (non-Finnish) · 6,685/1,179,030 alleles
Filtering AF
0.556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.551%
Overall
0.453%
7,311/1,612,704 alleles · rare
exomes 6,814/1,460,388 · genomes 497/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.567% | 176 |
| Remaining individualsnot grpmax-eligible | 0.397% | 252 |
| Admixed American | 0.288% | 347 |
| Ashkenazi Jewishnot grpmax-eligible | 0.186% | 538 |
| African / African-American | 0.137% | 729 |
| Middle Eastern | 0.066% | 1,515 |
| Finnishnot grpmax-eligible | 0.0659% | 1,517 |
| South Asian | 0.0011% | 91,056 |
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.Ala348=
- Coding
- c.1044C>G
- MANE Select
- NM_145059
- dbSNP
- rs17880985
- Type
- single nucleotide variant
- Location
- chr16:70470402 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- FCSK p.Ala348Ser Uncertain significance ★★ ⚠ same residue
- FCSK p.Ala348fs Conflicting classifications of pathogenicity ★ 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.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-ala348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown