AK2 c.498+18A>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
reticular dysgenesis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +18 | near-intronic (+18 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.69 | GERP -3.4 |
| Non-coding constraint | Z 1.32 | 1 kb window · o/e 0.91 · regional · uncalibrated |
| Overall | ||
| CADD | 12.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AK2
- Coding
- c.498+18A>C
- MANE Select
- NM_001625
- Type
- single nucleotide variant
- Location
- chr1:33014504 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.49 · 3 PDB
Disease context
reticular dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Reticular dysgenesis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- <1 / 1 000 000 (Europe)
Similar variants
- AK2 c.330+5G>A Pathogenic ★★ same condition
- AK2 c.498+1G>A Pathogenic/Likely pathogenic ★★ same condition
- AK2 p.Ala182Asp Pathogenic/Likely pathogenic ★★ same condition
- AK2 p.Arg103Trp Pathogenic/Likely pathogenic ★★ same condition
- AK2 p.Arg175Pro Likely pathogenic ★★ same condition
- AK2 p.Met1Val Pathogenic ★★ same condition
- AK2 p.Ala212Thr Uncertain significance ★★ ⚠ same condition
- AK2 p.Ala2Val Uncertain significance ★★ ⚠ same condition
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/ak2-c-498-plus-18a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown