Is ADA2 p.Phe80fs (c.239del) pathogenic?

ADA2 p.Phe80fs (c.239del) is classified Pathogenic in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-16). Absent from gnomAD; Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Phe80fs (c.239del)?

ADA2 p.Phe80fs (c.239del) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Phe80fs (c.239del) in the general population?

ADA2 p.Phe80fs (c.239del) 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.Phe80fs

c.239del · rs2517360414 · VCV2005909

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.82	GERP -2.8, 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: ADA2
Protein: p.Phe80fs
Coding: c.239del
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs2517360414
Type: Deletion
Location: chr22:17209439 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 80: the sant domain; an α-helix

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

ADA2 p.Ala221fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Asn53fs Pathogenic ★★ same condition
ADA2 p.His434_Pro435insTer Pathogenic ★★ same condition
ADA2 p.Lys314fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Lys466fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Tyr353fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 c.754-12del Likely benign ★★ same condition
ADA2 c.882-11del Benign/Likely benign ★★ 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-phe80fs (accessed [today's date]).

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