Is ADA2 p.Asp347fs (c.1040del) pathogenic?

ADA2 p.Asp347fs (c.1040del) is classified Pathogenic in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-14). No gnomAD frequency available for this variant; Associated with Sneddon syndrome.

What condition is associated with ADA2 p.Asp347fs (c.1040del)?

ADA2 p.Asp347fs (c.1040del) is associated with Sneddon syndrome (ClinVar).

How common is ADA2 p.Asp347fs (c.1040del) in the general population?

ADA2 p.Asp347fs (c.1040del) is no gnomAD frequency available for this variant (gnomAD).

How is Sneddon syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ADA2 p.Asp347fs

c.1040del · rs2062064773 · VCV1033820

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

Sneddon syndrome

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 -1.3	GERP -3

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.Asp347fs
Coding: c.1040del
MANE Select: NM_001282225
dbSNP: rs2062064773
Type: Deletion
Location: chr22:17188380 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

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

Disease context

Sneddon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sneddon syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ADA2 p.Ala221fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Lys314fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Lys466fs Pathogenic/Likely pathogenic ★★ same condition
ADA2 c.754-12del Likely benign ★★ same condition
ADA2 p.Asp347Asn Uncertain significance ★ ⚠ same residue
ADA2 c.973-2A>G Pathogenic ★★ same condition
ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Arg169Trp 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-asp347fs (accessed [today's date]).

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