Is ADA p.Val178fs (c.532dup) pathogenic?

ADA p.Val178fs (c.532dup) is classified Pathogenic in ADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-08-10). Ultra-rare (gnomAD MAF 6.704e-06); 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.Val178fs (c.532dup) in the general population?

ADA p.Val178fs (c.532dup) is ultra-rare (gnomAD MAF 6.704e-06) (gnomAD).

ADA p.Val178fs

Q: What condition is associated with ADA p.Val178fs (c.532dup)?

ADA p.Val178fs (c.532dup) 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.532dup · rs886041796 · VCV280626

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 6.704e-06)

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 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.00067% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ADA
Protein: p.Val178fs
Coding: c.532dup
MANE Select: NM_000022
dbSNP: rs886041796
Type: Duplication
Location: chr20:44624275 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 178: a β-strand

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.Val178= Benign/Likely benign ★★ same residue
ADA p.Val133fs Pathogenic ★★★ same condition
ADA p.Asn285fs Pathogenic/Likely pathogenic ★★ same condition
ADA p.Glu217fs Pathogenic ★★ same condition
ADA p.Leu193fs Pathogenic/Likely pathogenic ★★ same condition
ADA p.Leu231fs Pathogenic/Likely pathogenic ★★ same condition
ADA p.Asn293delinsThrGlyTer Pathogenic ★ same condition
ADA p.Gln119fs 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-val178fs (accessed [today's date]).

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