PDK2 p.Arg74=
c.220C>A · rs35550088 · VCV777201
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.05%, 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 1.9 | GERP -4.4, phastCons 1 |
| Overall | ||
| CADD | 9.321 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.05%
African / African-American · 1,537/75,032 alleles
Filtering AF
1.96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.93%
Overall
0.11%
1,782/1,613,800 alleles · low-frequency
exomes 866/1,461,516 · genomes 916/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.05% | 49 |
| Remaining individualsnot grpmax-eligible | 0.154% | 651 |
| Admixed American | 0.127% | 790 |
| Middle Eastern | 0.066% | 1,515 |
| European (non-Finnish) | 0.00559% | 17,879 |
| South Asian | 0.00329% | 30,358 |
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
- PDK2
- Protein
- p.Arg74=
- Coding
- c.220C>A
- MANE Select
- NM_002611
- dbSNP
- rs35550088
- Type
- single nucleotide variant
- Location
- chr17:50097524 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.16 · 38 PDB
- Residue 74
- an α-helix
Similar variants
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- PDK2 p.Ala378Val Uncertain significance ★ ⚠ same type
- PDK2 p.Arg162Cys Uncertain significance ★ ⚠ same type
- PDK2 p.Arg291Gln Uncertain significance ★ ⚠ same type
- PDK2 p.Arg405Cys Uncertain significance ★ ⚠ same type
- PDK2 p.Asn69Lys Uncertain significance ★ ⚠ same type
- PDK2 p.Asp114Gly Uncertain significance ★ ⚠ same type
- PDK2 p.Asp143Asn 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/pdk2-p-arg74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown