Is AK2 p.Gly205fs (c.614_615del) pathogenic?

AK2 p.Gly205fs (c.614615del) is classified Likely pathogenic in AK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-09). Very rare (popmax 0.00551%, nfe); Associated with reticular dysgenesis.

What condition is associated with AK2 p.Gly205fs (c.614_615del)?

AK2 p.Gly205fs (c.614_615del) is associated with reticular dysgenesis (ClinVar).

How common is AK2 p.Gly205fs (c.614_615del) in the general population?

AK2 p.Gly205fs (c.614_615del) is very rare (popmax 0.00551%, nfe) (gnomAD).

How is Reticular dysgenesis inherited?

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

AK2 p.Gly205fs

c.614_615del · rs746465070 · VCV1067803

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

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 6.2	GERP 2.8, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% European (non-Finnish) · 65/1,180,026 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00415% 67/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,154
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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: AK2
Protein: p.Gly205fs
Coding: c.614_615del
MANE Select: NM_001625
dbSNP: rs746465070
Type: Deletion
Location: chr1:33013286 (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.Gly205= Likely benign ★★ same residue
AK2 p.Gly205Glu Uncertain significance ★★ ⚠ same residue
AK2 p.Ala212_Ter240delinsXaa 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-gly205fs (accessed [today's date]).

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