Is AK2 p.Ile239fs (c.714dup) pathogenic?

AK2 p.Ile239fs (c.714dup) is classified Uncertain significance in AK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-02). Absent from gnomAD; Associated with reticular dysgenesis.

What condition is associated with AK2 p.Ile239fs (c.714dup)?

AK2 p.Ile239fs (c.714dup) is associated with reticular dysgenesis (ClinVar).

How common is AK2 p.Ile239fs (c.714dup) in the general population?

AK2 p.Ile239fs (c.714dup) is absent from gnomAD (gnomAD).

How is Reticular dysgenesis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AK2 p.Ile239fs

c.714dup · rs2124278051 · VCV1384263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

reticular dysgenesis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 2.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AK2
Protein: p.Ile239fs
Coding: c.714dup
MANE Select: NM_001625
dbSNP: rs2124278051
Type: Duplication
Location: chr1:33013186 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 3 PDB

Full AK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

reticular dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Reticular dysgenesis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

AK2 p.Gly29fs Pathogenic/Likely pathogenic ★★ same condition
AK2 c.220-2dup Uncertain significance ★★ same condition
AK2 p.Val236_Met237insIle Uncertain significance ★ same condition
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

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-p-ile239fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown