Is ADA2 p.Met477fs (c.1430dup) pathogenic?

ADA2 p.Met477fs (c.1430dup) is classified Pathogenic in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Absent from gnomAD; Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Met477fs (c.1430dup)?

ADA2 p.Met477fs (c.1430dup) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Met477fs (c.1430dup) in the general population?

ADA2 p.Met477fs (c.1430dup) 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.Met477fs

c.1430dup · rs2061972270 · VCV961329

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 -0.54	GERP -2.9, phastCons 0.002

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.Met477fs
Coding: c.1430dup
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs2061972270
Type: Duplication
Location: chr22:17181831 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

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.Met477Thr Uncertain significance ★★ ⚠ same residue
ADA2 p.Met477Ile Uncertain significance ★ ⚠ same residue
ADA2 p.Ala427fs Likely pathogenic ★ same condition
ADA2 p.Arg49fs Pathogenic ★ same condition
ADA2 p.Gly25fs Likely pathogenic ★ same condition
ADA2 p.Asn491fs Conflicting classifications of pathogenicity ★ same condition
ADA2 p.Thr380dup Conflicting classifications of pathogenicity ★ same condition
ADA2 c.973-20_973-16dup 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-met477fs (accessed [today's date]).

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