CAST p.Leu318=
c.954G>A · rs529588489 · VCV2718808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.264 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 17.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
European (non-Finnish) · 124/1,179,288 alleles
Filtering AF
0.00901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00842%
Overall
0.00837%
135/1,613,294 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0105% | 9,510 |
| Admixed American | 0.00833% | 12,003 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,492 |
| African / African-American | 0.00133% | 75,022 |
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.Leu318=
- Coding
- c.954G>A
- dbSNP
- rs529588489
- Type
- single nucleotide variant
- Location
- chr5:96741301 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.67
- Residue 318
- the 'disordered' region
Similar variants
- PCSK1 p.Asp318Tyr 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-leu318 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown