CD28 p.Ala35=
c.105G>A · rs41272649 · VCV774413
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.38%, nfe)
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 -1.8 | GERP -4.6 |
| Overall | ||
| CADD | 1.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.38%
European (non-Finnish) · 16,305/1,179,966 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.36%
Overall
1.13%
18,260/1,613,932 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.38% | 72 |
| Remaining individualsnot grpmax-eligible | 1.23% | 81 |
| Finnishnot grpmax-eligible | 1% | 100 |
| Admixed American | 0.443% | 226 |
| Ashkenazi Jewishnot grpmax-eligible | 0.24% | 417 |
| African / African-American | 0.207% | 484 |
| Middle Eastern | 0.115% | 866 |
| South Asian | 0.0516% | 1,937 |
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
- CD28
- Protein
- p.Ala35=
- Coding
- c.105G>A
- MANE Select
- NM_006139
- dbSNP
- rs41272649
- Type
- single nucleotide variant
- Location
- chr2:203726685 (GRCh38)
- Gene constraint
- LOEUF 0.634 · pLI 0.78 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 10 PDB
- Residue 35
- a β-strand; the ig-like v-type domain
Similar variants
- CD28 p.Arg203Cys Uncertain significance ★ same type
- CD28 p.Asn19Asp Uncertain significance ★ ⚠ same type
- CD28 p.Asn45Ser Uncertain significance ★ ⚠ same type
- CD28 p.Gln15Arg Uncertain significance ★ ⚠ same type
- CD28 p.Glu93Lys Uncertain significance ★ ⚠ same type
- CD28 p.Gly83Arg Uncertain significance ★ ⚠ same type
- CD28 p.Gly88Ala Uncertain significance ★ ⚠ same type
- CD28 p.Ile176Phe 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/cd28-p-ala35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown