Is ADA2 p.Glu234= (c.702G>A) pathogenic?

ADA2 p.Glu234= (c.702G>A) is classified Likely benign in ADA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-02). Ultra-rare (popmax 0.0275%, sas); Associated with Sneddon syndrome.

What condition is associated with ADA2 p.Glu234= (c.702G>A)?

ADA2 p.Glu234= (c.702G>A) is associated with Sneddon syndrome, deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Glu234= (c.702G>A) in the general population?

ADA2 p.Glu234= (c.702G>A) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

How is Sneddon syndrome inherited?

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

ADA2 p.Glu234=

c.702G>A · rs528271447 · VCV1454072

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Conditions

Sneddon syndrome

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 -0.098	GERP -1.3, phastCons 0.89
Overall
CADD	7.001	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% South Asian · 25/91,056 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0167% 270/1,613,722 alleles · ultra-rare exomes 262/1,461,360 · genomes 8/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,642
European (non-Finnish)	0.02%	5,000
Remaining individualsnot grpmax-eligible	0.0064%	15,613
Admixed American	0.005%	20,005
African / African-American	0.00266%	37,534

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: ADA2
Protein: p.Glu234=
Coding: c.702G>A
MANE Select: NM_001282225
dbSNP: rs528271447
Type: single nucleotide variant
Location: chr22:17203614 (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

Also linked: deficiency of adenosine deaminase 2

For Sneddon syndrome (Orphanet):

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

Similar variants

ADA2 c.754-2A>G Likely pathogenic ★★ same condition
ADA2 c.882-2A>G Pathogenic ★★ same condition
ADA2 c.973-2A>G Pathogenic ★★ same condition
ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Arg169Trp Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Arg306Ter Likely pathogenic ★★ same condition
ADA2 p.Arg312Ter Pathogenic ★★ same condition
ADA2 p.Asn370Lys 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-glu234 (accessed [today's date]).

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