FCSK p.Val693=
c.2079C>A · rs745471444 · VCV2781012
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00249%, 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 -0.33 | GERP -0.62, phastCons 0.073 |
| Overall | ||
| CADD | 6.913 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00249%
European (non-Finnish) · 29/1,166,730 alleles
Filtering AF
0.00174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00151%
Overall
0.00189%
30/1,586,926 alleles · very rare
exomes 28/1,434,676 · genomes 2/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00249% | 40,232 |
| African / African-American | 0.00134% | 74,570 |
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.Val693=
- Coding
- c.2079C>A
- MANE Select
- NM_145059
- dbSNP
- rs745471444
- Type
- single nucleotide variant
- Location
- chr16:70474618 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- 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
- FCSK p.Ala554Val 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-val693 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown