CAST p.Ser216=
c.648A>G · rs1181134741 · VCV1944296
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.03 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.86 | GERP -3.3 |
| Overall | ||
| CADD | 0.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
African / African-American · 5/74,860 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00162%
Overall
0.000372%
6/1,612,236 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00668% | 14,972 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
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.Ser216=
- Coding
- c.648A>G
- dbSNP
- rs1181134741
- Type
- single nucleotide variant
- Location
- chr5:96736189 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.67
- Residue 216
- the 'disordered' region
Similar variants
- 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
- CAST p.Ser231Leu 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-ser216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown