CASS4 p.Leu71=
c.213C>T · rs34102676 · VCV778896
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.79%, afr)
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 0.27 | GERP -3.2, phastCons 0.009 |
| Overall | ||
| CADD | 7.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.79%
African / African-American · 2,847/75,054 alleles
Filtering AF
3.68%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.63%
Overall
0.241%
3,885/1,614,066 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.79% | 26 |
| Middle Eastern | 0.627% | 160 |
| Admixed American | 0.497% | 201 |
| Remaining individualsnot grpmax-eligible | 0.443% | 226 |
| European (non-Finnish) | 0.0346% | 2,892 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0304% | 3,288 |
| South Asian | 0.00879% | 11,381 |
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.Leu71=
- Coding
- c.213C>T
- MANE Select
- NM_020356
- dbSNP
- rs34102676
- Type
- single nucleotide variant
- Location
- chr20:56437340 (GRCh38)
- Gene constraint
- LOEUF 0.53 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 58.88 · 1 PDB
- Residue 71
- the sh3 domain
Similar variants
- CASS4 p.Arg491Lys 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
- CASS4 p.Ala682Val 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-leu71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown