CASS4 p.Pro134=
c.402C>T · VCV3485355
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0675%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -4.7 |
| Overall | ||
| CADD | 1.273 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0675%
East Asian · 30/44,472 alleles
Filtering AF
0.0485%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0421%
Overall
0.00355%
56/1,578,720 alleles · ultra-rare
exomes 53/1,426,384 · genomes 3/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0675% | 1,482 |
| Admixed American | 0.0075% | 13,328 |
| South Asian | 0.00459% | 21,763 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00368% | 27,186 |
| African / African-American | 0.00272% | 36,812 |
| European (non-Finnish) | 0.00129% | 77,531 |
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
- CASS4
- Protein
- p.Pro134=
- Coding
- c.402C>T
- MANE Select
- NM_020356
- Type
- single nucleotide variant
- Location
- chr20:56437529 (GRCh38)
- Gene constraint
- LOEUF 0.53 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 58.88 · 1 PDB
Similar variants
- CASS4 p.Arg491Lys Benign ★★ same type
- CASS4 p.Leu71= Benign ★★ same type
- CASS4 p.Ser426Leu Benign ★★ same type
- CASS4 p.Ala10Val Uncertain significance ★ ⚠ same type
- CASS4 p.Ala16Asp Uncertain significance ★ ⚠ same type
- CASS4 p.Ala271Thr Uncertain significance ★ ⚠ same type
- CASS4 p.Ala377Val Uncertain significance ★ ⚠ same type
- CASS4 p.Ala456Thr 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/cass4-p-pro134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown