CAST p.Pro727=
c.2181T>G · rs79522948 · VCV708906
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.4%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.025 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.89 | GERP -3.6 |
| Overall | ||
| CADD | 1.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.4%
African / African-American · 1,053/74,952 alleles
Filtering AF
1.33%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.31%
Overall
0.0726%
1,170/1,610,832 alleles · low-frequency
exomes 578/1,458,504 · genomes 592/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.4% | 71 |
| Remaining individualsnot grpmax-eligible | 0.101% | 990 |
| Admixed American | 0.0767% | 1,304 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.0011% | 91,000 |
| European (non-Finnish) | 0.00051% | 196,182 |
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
- CAST
- Protein
- p.Pro727=
- Coding
- c.2181T>G
- dbSNP
- rs79522948
- Type
- single nucleotide variant
- Location
- chr5:96767912 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.67
Similar variants
- PCSK1 p.Val727Ile Uncertain significance ★ ⚠ same residue
- PCSK1 p.Lys286Ter Pathogenic/Likely pathogenic ★★ same type
- CAST p.Ala329Gly Uncertain significance ★★ ⚠ same type
- CAST p.Asp160Val Uncertain significance ★★ ⚠ same type
- CAST p.Gln731His Uncertain significance ★★ ⚠ same type
- CAST p.Glu296Gly Uncertain significance ★★ ⚠ same type
- CAST p.Ile274Val Uncertain significance ★★ ⚠ same type
- CAST p.Leu586Pro 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/cast-p-pro727 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown