Is ADA2 p.Gly47Arg (c.139G>C) pathogenic?

ADA2 p.Gly47Arg (c.139G>C) is classified Pathogenic in ADA2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-01). AlphaMissense: likely pathogenic (0.8966); Ultra-rare (popmax 0.011%, sas); Associated with Sneddon syndrome.

What condition is associated with ADA2 p.Gly47Arg (c.139G>C)?

ADA2 p.Gly47Arg (c.139G>C) is associated with Sneddon syndrome, deficiency of adenosine deaminase 2, autoinflammatory syndrome (ClinVar).

How common is ADA2 p.Gly47Arg (c.139G>C) in the general population?

ADA2 p.Gly47Arg (c.139G>C) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is Sneddon syndrome inherited?

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

What do computational predictors say about ADA2 p.Gly47Arg (c.139G>C)?

AlphaMissense predicts likely pathogenic (score 0.8966) — an in-silico prediction, not a clinical call.

ADA2 p.Gly47Arg

c.139G>C · rs202134424 · VCV1076271

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.8966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Sneddon syndrome

Computational evidence

Protein change
AlphaMissense	0.8966	likely pathogenic ✓ concordant with ClinVar
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -15.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.98
Overall
CADD	19.28	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,082 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00211% 34/1,613,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
Admixed American	0.00667%	14,993
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00267%	37,456
European (non-Finnish)	0.00136%	73,752

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.Gly47Arg
Coding: c.139G>C
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs202134424
Type: single nucleotide variant
Location: chr22:17209539 (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 autoinflammatory syndrome

For Sneddon syndrome (Orphanet):

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

Similar variants

ADA2 p.Gly47Ala Pathogenic ★★ ⚠ same residue
ADA2 p.Gly47Trp Pathogenic ★★ same residue
ADA2 p.Gly47Val Pathogenic/Likely pathogenic ★★ same residue
ADA2 p.Gly47Glu Likely pathogenic ★ same residue
ADA2 p.Gly47= Likely benign ★ same residue
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

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-gly47arg (accessed [today's date]).

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