Is ADA2 p.Lys511Gln (c.1531A>C) pathogenic?

ADA2 p.Lys511Gln (c.1531A>C) is classified Uncertain significance in ADA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0156%, eas); Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Lys511Gln (c.1531A>C)?

ADA2 p.Lys511Gln (c.1531A>C) is associated with deficiency of adenosine deaminase 2, Sneddon syndrome (ClinVar).

How common is ADA2 p.Lys511Gln (c.1531A>C) in the general population?

ADA2 p.Lys511Gln (c.1531A>C) is ultra-rare (popmax 0.0156%, eas) (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.Lys511Gln (c.1531A>C)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

ADA2 p.Lys511Gln

c.1531A>C · rs535337577 · VCV474907

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

deficiency of adenosine deaminase 2

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.66	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 -3.8	GERP -2
Overall
CADD	1.894	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 0.0156% East Asian · 7/44,854 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000995% 16/1,608,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,408
Remaining individualsnot grpmax-eligible	0.0016%	62,322
European (non-Finnish)	0.000681%	146,812

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.Lys511Gln
Coding: c.1531A>C
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs535337577
Type: single nucleotide variant
Location: chr22:17181488 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

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

Also linked: Sneddon syndrome

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-lys511gln (accessed [today's date]).

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