Is ADA2 p.Arg306Gln (c.917G>A) pathogenic?

ADA2 p.Arg306Gln (c.917G>A) is classified Uncertain significance in ADA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00223%, eas); Associated with Sneddon syndrome.

What condition is associated with ADA2 p.Arg306Gln (c.917G>A)?

ADA2 p.Arg306Gln (c.917G>A) is associated with Sneddon syndrome, deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Arg306Gln (c.917G>A) in the general population?

ADA2 p.Arg306Gln (c.917G>A) is very rare (popmax 0.00223%, eas) (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.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

ADA2 p.Arg306Gln

c.917G>A · rs768927379 · VCV1436425

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Sneddon syndrome

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -2.4
Overall
CADD	0.366	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0013% 21/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
South Asian	0.0022%	45,537
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00136%	73,744
African / African-American	0.00133%	74,928

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs768927379
Type: single nucleotide variant
Location: chr22:17189997 (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 p.Arg306Ter Likely pathogenic ★★ same residue
ADA2 p.Arg306Gly Uncertain significance ★★ ⚠ 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
ADA2 p.Arg312Ter 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-arg306gln (accessed [today's date]).

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