Is ADA p.Val178= (c.534A>G) pathogenic?

ADA p.Val178= (c.534A>G) is classified Benign/Likely benign in ADA (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 41.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency.

ADA p.Val178=

Q: What condition is associated with ADA p.Val178= (c.534A>G)?

ADA p.Val178= (c.534A>G) 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 common is ADA p.Val178= (c.534A>G) in the general population?

ADA p.Val178= (c.534A>G) is common (popmax 41.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.534A>G · rs244076 · VCV254716

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 41.9%, afr) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -2.6, phastCons 1
Overall
CADD	7.879	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41.9% African / African-American · 31,392/74,906 alleles

Filtering AF 41.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.4%

Overall 18.8% 303,107/1,613,656 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	41.9%	2
South Asian	24.5%	4
Middle Eastern	22.4%	4
Remaining individualsnot grpmax-eligible	20.2%	5
Admixed American	19.9%	5
Ashkenazi Jewishnot grpmax-eligible	18.5%	5
European (non-Finnish)	17.2%	6
Finnishnot grpmax-eligible	15.5%	6
East Asian	12.2%	8
Amishnot grpmax-eligible	11.3%	9

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADA
Protein: p.Val178=
Coding: c.534A>G
MANE Select: NM_000022
dbSNP: rs244076
Type: single nucleotide variant
Location: chr20:44624274 (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.Val178fs Pathogenic ★★ same residue
ADA c.1078+2T>A Likely pathogenic ★★★ same condition
ADA c.219-2A>G Likely pathogenic ★★★ same condition
ADA c.363-2A>G Likely pathogenic ★★★ same condition
ADA c.606+1G>T Likely pathogenic ★★★ same condition
ADA c.975+1G>A Pathogenic ★★★ same condition
ADA c.976-1G>C Pathogenic ★★★ same condition
ADA p.Ala329Val 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-val178 (accessed [today's date]).

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