Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor loss, 37 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -0.042 |
| Overall | ||
| CADD | 0.907 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,754/44,754 alleles
Filtering AF
99.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 99.8%
Overall
99.9%
1,586,121/1,587,174 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| Finnishnot grpmax-eligible | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| South Asian | 100% | 1 |
| European (non-Finnish) | 100% | 1 |
| Admixed American | 99.9% | 1 |
| Remaining individualsnot grpmax-eligible | 99.9% | 1 |
| Middle Eastern | 99.9% | 1 |
| African / African-American | 98.8% | 1 |
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
- CD96
- Protein
- p.Pro454=
- Coding
- c.1362G>C
- MANE Select
- NM_005816
- dbSNP
- rs1533270
- Type
- single nucleotide variant
- Location
- chr3:111637236 (GRCh38)
- Gene constraint
- LOEUF 1.16 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.81 · 1 PDB
- Residue 454
- the 'disordered' region
Similar variants
- CD96 c.1249+1G>A Uncertain significance ★★ same type
- CD96 c.544-1512C>T Uncertain significance ★★ ⚠ same type
- CD96 p.Asp205Gly Uncertain significance ★★ ⚠ same type
- CD96 p.Asp224Asn Uncertain significance ★★ ⚠ same type
- CD96 p.Ile151Thr Uncertain significance ★★ ⚠ same type
- CD96 p.Leu120Pro Uncertain significance ★★ ⚠ same type
- CD96 p.Lys500Arg Uncertain significance ★★ ⚠ same type
- CD96 p.Pro346Ser 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/cd96-p-pro454 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown