CASD1 p.Val456=
c.1368A>G · VCV3485084
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0813%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.82 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 6.554 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0813%
African / African-American · 61/75,020 alleles
Filtering AF
0.0649%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.059%
Overall
0.00484%
78/1,613,196 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0813% | 1,230 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,490 |
| Admixed American | 0.00667% | 14,995 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
| European (non-Finnish) | 0.000593% | 168,495 |
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
- CASD1
- Protein
- p.Val456=
- Coding
- c.1368A>G
- MANE Select
- NM_022900
- Type
- single nucleotide variant
- Location
- chr7:94544422 (GRCh38)
- Gene constraint
- LOEUF 0.617 · pLI 0.34 (gnomAD)
- Structure
- AlphaFold pLDDT 87.87
Similar variants
- SGCE c.232+1G>T Pathogenic/Likely pathogenic ★★ same type
- SGCE c.391-1G>A Pathogenic ★★ same type
- SGCE c.825+1G>T Pathogenic/Likely pathogenic ★★ same type
- SGCE p.Arg102Ter Pathogenic ★★ same type
- SGCE p.Arg237Ter Pathogenic ★★ same type
- SGCE p.Arg342Ter Pathogenic/Likely pathogenic ★★ same type
- SGCE p.Arg372Ter Pathogenic ★★ same type
- SGCE p.Arg97Ter Pathogenic ★★ 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/casd1-p-val456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown