Is ADA2 p.Gly47Val (c.140G>T) pathogenic?

ADA2 p.Gly47Val (c.140G>T) is classified Pathogenic/Likely pathogenic in ADA2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.89); Ultra-rare (popmax 0.0329%, mid); Associated with ADA2-related disorder.

What condition is associated with ADA2 p.Gly47Val (c.140G>T)?

ADA2 p.Gly47Val (c.140G>T) is associated with ADA2-related disorder, Sneddon syndrome, deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Gly47Val (c.140G>T) in the general population?

ADA2 p.Gly47Val (c.140G>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ADA2 p.Gly47Val (c.140G>T)?

AlphaMissense predicts likely pathogenic (score 0.89) — an in-silico prediction, not a clinical call.

ADA2 p.Gly47Val

c.140G>T · rs200930463 · VCV120306

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely pathogenic

0.89 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ADA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.89	likely pathogenic ✓ concordant with ClinVar
REVEL	0.909	moderately pathogenic-leaning
SaProt	LLR -16.05	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 4.5	GERP 0.66, phastCons 0.99
Overall
CADD	21.5	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00297% 48/1,613,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
South Asian	0.00769%	13,012
Admixed American	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0048%	20,826
European (non-Finnish)	0.00263%	38,053
East Asian	0.00223%	44,884

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.Gly47Val
Coding: c.140G>T
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs200930463
Type: single nucleotide variant
Location: chr22:17209538 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

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

Disease context

ADA2-related disorder

Also linked: Sneddon syndrome deficiency of adenosine deaminase 2

Similar variants

ADA2 p.Gly47Ala Pathogenic ★★ ⚠ same residue
ADA2 p.Gly47Arg Pathogenic ★★ same residue
ADA2 p.Gly47Trp 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-gly47val (accessed [today's date]).

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