Is ADA2 p.Arg171Trp (c.511C>T) pathogenic?

ADA2 p.Arg171Trp (c.511C>T) is classified Benign/Likely benign in ADA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.1142); Low-frequency (popmax 1.61%, afr); Associated with autoinflammatory syndrome.

What condition is associated with ADA2 p.Arg171Trp (c.511C>T)?

ADA2 p.Arg171Trp (c.511C>T) is associated with autoinflammatory syndrome, deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Arg171Trp (c.511C>T) in the general population?

ADA2 p.Arg171Trp (c.511C>T) is low-frequency (popmax 1.61%, afr) (gnomAD).

What do computational predictors say about ADA2 p.Arg171Trp (c.511C>T)?

AlphaMissense predicts likely benign (score 0.1142) — an in-silico prediction, not a clinical call.

ADA2 p.Arg171Trp

c.511C>T · rs115986203 · VCV541741

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1142 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.61%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
AlphaMissense	0.1142	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -9.56	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 -0.51	GERP -3.2
Overall
CADD	14.58	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 1.61% African / African-American · 1,210/75,044 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.0851% 1,374/1,614,156 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.61%	62
Remaining individualsnot grpmax-eligible	0.114%	880
Admixed American	0.0966%	1,035
Middle Eastern	0.033%	3,031
Finnishnot grpmax-eligible	0.00625%	16,009
South Asian	0.00439%	22,771
East Asian	0.00223%	44,890
European (non-Finnish)	0.00203%	49,166

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.Arg171Trp
Coding: c.511C>T
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs115986203
Type: single nucleotide variant
Location: chr22:17207102 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: deficiency of adenosine deaminase 2

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-arg171trp (accessed [today's date]).

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