FCSK p.His560=
c.1680C>T · rs759951573 · VCV2956939
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00835%, sas)
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 -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.164 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00835%
South Asian · 7/83,806 alleles
Filtering AF
0.00386%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00272%
Overall
0.00209%
32/1,532,146 alleles · very rare
exomes 29/1,379,954 · genomes 3/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00835% | 11,972 |
| African / African-American | 0.00275% | 36,417 |
| European (non-Finnish) | 0.00192% | 51,976 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,524 |
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.His560=
- Coding
- c.1680C>T
- MANE Select
- NM_145059
- dbSNP
- rs759951573
- Type
- single nucleotide variant
- Location
- chr16:70473256 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- FCSK p.His560fs 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-his560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown