Is ADA2 p.Asp261= (c.783C>T) pathogenic?

ADA2 p.Asp261= (c.783C>T) is classified Likely benign in ADA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-31). Rare (popmax 0.308%, afr); Associated with Sneddon syndrome.

What condition is associated with ADA2 p.Asp261= (c.783C>T)?

ADA2 p.Asp261= (c.783C>T) is associated with Sneddon syndrome, deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Asp261= (c.783C>T) in the general population?

ADA2 p.Asp261= (c.783C>T) is rare (popmax 0.308%, afr) (gnomAD).

How is Sneddon syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ADA2 p.Asp261=

c.783C>T · rs150249309 · VCV720161

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.308%, afr)

Conditions

Sneddon syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP 0.36
Overall
CADD	3.275	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.308% African / African-American · 231/74,974 alleles

Filtering AF 0.275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.263%

Overall 0.0159% 257/1,613,492 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.308%	325
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Admixed American	0.00834%	11,996
European (non-Finnish)	0.000424%	235,957

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.Asp261=
Coding: c.783C>T
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs150249309
Type: single nucleotide variant
Location: chr22:17191781 (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 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-asp261 (accessed [today's date]).

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