CAST p.Ser74Cys
c.221C>G · VCV4219521
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.264%, mid)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.11 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP 0.61, phastCons 0.026 |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.264%
Middle Eastern · 16/6,062 alleles
Filtering AF
0.165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.135%
Overall
0.000992%
16/1,612,746 alleles · rare
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.Ser74Cys
- Coding
- c.221C>G
- Type
- single nucleotide variant
- Location
- chr5:96722649 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.67
- Residue 74
- the 'disordered' region
Similar variants
- CAST p.Ala329Gly Uncertain significance ★★ ⚠ same condition
- CAST p.Asp160Val Uncertain significance ★★ ⚠ same condition
- CAST p.Gln731His Uncertain significance ★★ ⚠ same condition
- CAST p.Glu296Gly Uncertain significance ★★ ⚠ same condition
- CAST p.Ile274Val Uncertain significance ★★ ⚠ same condition
- CAST p.Leu586Pro Uncertain significance ★★ ⚠ same condition
- CAST p.Ser231Leu Uncertain significance ★★ ⚠ same condition
- PCSK1 p.Asp176Asn Uncertain significance ★★ ⚠ same condition
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-ser74cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown