Is ADA2 p.Ala109Asp (c.326C>A) pathogenic?

ADA2 p.Ala109Asp (c.326C>A) is classified Pathogenic in ADA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-03-06). AlphaMissense: likely pathogenic (0.9507); Absent from gnomAD v4.1; Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Ala109Asp (c.326C>A)?

ADA2 p.Ala109Asp (c.326C>A) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Ala109Asp (c.326C>A) in the general population?

ADA2 p.Ala109Asp (c.326C>A) is absent from gnomAD v4.1 (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.Ala109Asp (c.326C>A)?

AlphaMissense predicts likely pathogenic (score 0.9507) — an in-silico prediction, not a clinical call.

ADA2 p.Ala109Asp

c.326C>A · rs587777240 · VCV120300

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9507 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

deficiency of adenosine deaminase 2

Computational evidence

Protein change
AlphaMissense	0.9507	likely pathogenic ✓ concordant with ClinVar
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -13.02	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 5.6	GERP 1.5, phastCons 1
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADA2
Protein: p.Ala109Asp
Coding: c.326C>A
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs587777240
Type: single nucleotide variant
Location: chr22:17207287 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 109: the sant domain; an α-helix

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 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-ala109asp (accessed [today's date]).

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