Is ADA2 p.Arg34Gln (c.101G>A) pathogenic?

ADA2 p.Arg34Gln (c.101G>A) is classified Uncertain significance in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). AlphaMissense: likely benign (0.1185); Very rare (popmax 0.00401%, afr); Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Arg34Gln (c.101G>A)?

ADA2 p.Arg34Gln (c.101G>A) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Arg34Gln (c.101G>A) in the general population?

ADA2 p.Arg34Gln (c.101G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

How is Deficiency of adenosine deaminase 2 inherited?

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

What do computational predictors say about ADA2 p.Arg34Gln (c.101G>A)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

ADA2 p.Arg34Gln

c.101G>A · rs767960747 · VCV1404154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

deficiency of adenosine deaminase 2

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.5, phastCons 0.001
Overall
CADD	16.8	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 0.00401% African / African-American · 3/74,890 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000434% 7/1,613,944 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,963
South Asian	0.0011%	91,074
European (non-Finnish)	0.000254%	393,340

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.Arg34Gln
Coding: c.101G>A
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs767960747
Type: single nucleotide variant
Location: chr22:17209577 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 34: a binding site

Full ADA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

deficiency of adenosine deaminase 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Deficiency of adenosine deaminase 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ADA2 p.Arg34Pro Uncertain significance ★ ⚠ same residue
ADA2 p.Arg34Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
ADA2 p.Arg34= 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
ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ADA2 p.Arg169Trp 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-arg34gln (accessed [today's date]).

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