Is ADA2 p.Ile438Lys (c.1313_1314delinsAG) pathogenic?

ADA2 p.Ile438Lys (c.13131314delinsAG) is classified Uncertain significance in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-09). Absent from gnomAD; Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Ile438Lys (c.1313_1314delinsAG)?

ADA2 p.Ile438Lys (c.1313_1314delinsAG) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Ile438Lys (c.1313_1314delinsAG) in the general population?

ADA2 p.Ile438Lys (c.1313_1314delinsAG) is absent from gnomAD (gnomAD).

How is Deficiency of adenosine deaminase 2 inherited?

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

ADA2 p.Ile438Lys

c.1313_1314delinsAG · rs2517276454 · VCV2419957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

deficiency of adenosine deaminase 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1

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: ADA2
Protein: p.Ile438Lys
Coding: c.1313_1314delinsAG
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs2517276454
Type: Indel
Location: chr22:17181948 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 438: the swirm domain

Full ADA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

deficiency of adenosine deaminase 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Deficiency of adenosine deaminase 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

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ADA2 p.Trp501_Phe504delinsGluLeu Uncertain significance ★ same condition
ADA2 p.Tyr353Asn Uncertain significance ★ same condition
ADA2 c.1240-5_1240-4delinsGA Likely benign ★ same condition
ADA2 c.754-2A>G Likely pathogenic ★★ same condition
ADA2 c.882-2A>G Pathogenic ★★ same condition
ADA2 c.973-2A>G Pathogenic ★★ same condition
ADA2 p.Ala221fs Pathogenic/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/ada2-p-ile438lys (accessed [today's date]).

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