Is AK2 p.Ser213fs (c.636_*4953del) pathogenic?

AK2 p.Ser213fs (c.6364953del) is classified Pathogenic in AK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-01-01). Associated with reticular dysgenesis.

What condition is associated with AK2 p.Ser213fs (c.636_*4953del)?

AK2 p.Ser213fs (c.636_*4953del) is associated with reticular dysgenesis (ClinVar).

How is Reticular dysgenesis inherited?

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

AK2 p.Ser213fs

c.636_*4953del · VCV18250

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 0.17	GERP 0.005

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

Variant & gene context

Gene: AK2
Protein: p.Ser213fs
Coding: c.636_*4953del
MANE Select: NM_001625
Type: Deletion
Location: chr1:33008228 (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.Ser213Tyr Uncertain significance ★ same residue
AK2 p.Ala212_Ter240delinsXaa Likely pathogenic ★ same condition
AK2 p.Gly205fs Likely pathogenic ★ same condition
AK2 p.Tyr152fs Pathogenic ★ same condition
AK2 p.Asp113del Uncertain significance ★ same condition
AK2 c.220-5del Likely benign ★ same condition
AK2 c.426-17_426-14del Likely benign ★ same condition
AK2 p.Arg175fs 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-ser213fs (accessed [today's date]).

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