FCSK p.Pro180=
c.540G>A · rs370283040 · VCV2177706
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.306%, 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 -3.7 | GERP -3.1 |
| Overall | ||
| CADD | 1.213 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.306%
South Asian · 276/90,310 alleles
Filtering AF
0.276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.264%
Overall
0.0296%
476/1,610,400 alleles · rare
exomes 453/1,458,174 · genomes 23/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.306% | 327 |
| Remaining individualsnot grpmax-eligible | 0.0321% | 3,117 |
| European (non-Finnish) | 0.0146% | 6,853 |
| Admixed American | 0.00838% | 11,930 |
| African / African-American | 0.004% | 24,973 |
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.Pro180=
- Coding
- c.540G>A
- MANE Select
- NM_145059
- dbSNP
- rs370283040
- Type
- single nucleotide variant
- Location
- chr16:70467429 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.20
Similar variants
- FCSK p.Pro180Leu Uncertain significance ★ ⚠ same residue
- FCSK p.Pro180fs Likely pathogenic ★ 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
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-pro180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown