AKT2 p.Thr248=
c.744A>G · rs749826058 · VCV1337466
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, 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 -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.637 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,806 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00906%
Overall
0.00106%
17/1,607,244 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,343 |
| Admixed American | 0.0034% | 29,411 |
| South Asian | 0.00111% | 89,864 |
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
- AKT2
- Protein
- p.Thr248=
- Coding
- c.744A>G
- MANE Select
- NM_001626
- dbSNP
- rs749826058
- Type
- single nucleotide variant
- Location
- chr19:40238056 (GRCh38)
- Gene constraint
- LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.79 · 19 PDB
- Residue 248
- the protein kinase domain
Similar variants
- AKT2 c.709-3C>G Uncertain significance ★★ same type
- AKT2 c.960+3G>T Uncertain significance ★★ same type
- AKT2 p.Ala214Val Uncertain significance ★★ ⚠ same type
- AKT2 p.Arg113Trp Uncertain significance ★★ ⚠ same type
- AKT2 p.Arg15His Uncertain significance ★★ ⚠ same type
- AKT2 p.Arg253Gln Uncertain significance ★★ ⚠ same type
- AKT2 p.Arg347Cys Uncertain significance ★★ ⚠ same type
- AKT2 p.Asp399Asn 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/akt2-p-thr248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown