Is ADA p.Arg341fs (c.1021_1022del) pathogenic?

ADA p.Arg341fs (c.10211022del) is classified Pathogenic in ADA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-06). No gnomAD frequency available for this variant; Associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency.

How common is ADA p.Arg341fs (c.1021_1022del) in the general population?

ADA p.Arg341fs (c.1021_1022del) is no gnomAD frequency available for this variant (gnomAD).

ADA p.Arg341fs

Q: What condition is associated with ADA p.Arg341fs (c.1021_1022del)?

ADA p.Arg341fs (c.1021_1022del) is associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (ClinVar).

Q: How is Severe combined immunodeficiency due to adenosine deaminase deficiency inherited?

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

c.1021_1022del · rs2065317387 · VCV847778

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.38	GERP -3.1

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: ADA
Protein: p.Arg341fs
Coding: c.1021_1022del
MANE Select: NM_000022
dbSNP: rs2065317387
Type: Microsatellite
Location: chr20:44620355 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 341: an α-helix

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

Disease context

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to adenosine deaminase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ADA p.Arg341= Likely benign ★ same residue
ADA p.Glu337del Likely pathogenic ★★ same condition
ADA c.362+5_362+8del Likely pathogenic ★ same condition
ADA c.33+6CG[3] Likely benign ★ same condition
ADA c.34-29CT[3] Likely benign ★ same condition
ADA c.96-17_96-14del Likely benign ★ same condition
ADA c.479-3_479-2del Uncertain significance same condition
ADA c.1078+2T>A 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/ada-p-arg341fs (accessed [today's date]).

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