CD274 p.Ala121=
c.363C>A · rs35406529 · VCV738348
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.952%, 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 -9.4 | GERP -3.6 |
| Overall | ||
| CADD | 0.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.952%
African / African-American · 714/74,968 alleles
Filtering AF
0.894%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.871%
Overall
0.0505%
815/1,613,150 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.952% | 105 |
| Remaining individualsnot grpmax-eligible | 0.0752% | 1,329 |
| Admixed American | 0.0651% | 1,537 |
| Middle Eastern | 0.033% | 3,028 |
| South Asian | 0.00659% | 15,175 |
| European (non-Finnish) | 0.000594% | 168,470 |
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
- CD274
- Protein
- p.Ala121=
- Coding
- c.363C>A
- MANE Select
- NM_014143
- dbSNP
- rs35406529
- Type
- single nucleotide variant
- Location
- chr9:5457389 (GRCh38)
- Gene constraint
- LOEUF 0.476 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 88.13 · 78 PDB
- Residue 121
- a β-strand; the ig-like v-type domain
Similar variants
- CD274 c.*2635A>G Benign ★★ same type
- CD274 c.*93G>A Benign ★★ same type
- CD274 p.Arg186Ser Uncertain significance ★ ⚠ same type
- CD274 p.Asn183Thr Uncertain significance ★ ⚠ same type
- CD274 p.Asn278His Uncertain significance ★ ⚠ same type
- CD274 p.Glu205Asp Uncertain significance ★ ⚠ same type
- CD274 p.Glu217Lys Uncertain significance ★ ⚠ same type
- CD274 p.Met115Val 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/cd274-p-ala121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown