CD96 p.Ala178=
c.534A>G · rs759813586 · VCV2893110
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.143 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP -4.6, phastCons 0.22 |
| Overall | ||
| CADD | 8.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000744%
12/1,613,264 alleles · ultra-rare
exomes 11/1,461,032 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Admixed American | 0.00167% | 60,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,456 |
| European (non-Finnish) | 0.000763% | 131,038 |
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.Ala178=
- Coding
- c.534A>G
- MANE Select
- NM_005816
- dbSNP
- rs759813586
- Type
- single nucleotide variant
- Location
- chr3:111567638 (GRCh38)
- Gene constraint
- LOEUF 1.16 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.81 · 1 PDB
- Residue 178
- the ig-like v-type 2 domain
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-ala178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown