CAST p.Ser306=
c.918G>A · rs7724759 · VCV1274351
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 31.9%, nfe) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.027 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.32 | donor loss · deltas |
| Pangolin | Δ0.62 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 18.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
31.9%
European (non-Finnish) · 365,143/1,145,278 alleles
Filtering AF
31.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 31.8%
Overall
28.8%
453,548/1,575,622 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 31.9% | 3 |
| Amishnot grpmax-eligible | 31.8% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 30.4% | 3 |
| Middle Eastern | 28.7% | 3 |
| Remaining individualsnot grpmax-eligible | 28% | 4 |
| Finnishnot grpmax-eligible | 27% | 4 |
| South Asian | 23% | 4 |
| Admixed American | 18.7% | 5 |
| African / African-American | 10.4% | 10 |
| East Asian | 7.6% | 13 |
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.Ser306=
- Coding
- c.918G>A
- dbSNP
- rs7724759
- Type
- single nucleotide variant
- Location
- chr5:96740783 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.67
- Residue 306
- the 'disordered' region
Similar variants
- CAST p.Ser306Leu Conflicting classifications of pathogenicity ★ ⚠ 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-ser306 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown