Is ADA2 p.His260Gln (c.780T>G) pathogenic?

ADA2 p.His260Gln (c.780T>G) is classified Uncertain significance in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-11). AlphaMissense: likely benign (0.3231); Absent from gnomAD v4.1; Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.His260Gln (c.780T>G)?

ADA2 p.His260Gln (c.780T>G) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.His260Gln (c.780T>G) in the general population?

ADA2 p.His260Gln (c.780T>G) 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.His260Gln (c.780T>G)?

AlphaMissense predicts likely benign (score 0.3231) — an in-silico prediction, not a clinical call.

ADA2 p.His260Gln

c.780T>G · rs1269674261 · VCV2158101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

deficiency of adenosine deaminase 2

Computational evidence

Protein change
AlphaMissense	0.3231	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -2.7
Overall
CADD	6.433	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

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.His260Gln
Coding: c.780T>G
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs1269674261
Type: single nucleotide variant
Location: chr22:17191784 (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

For Deficiency of adenosine deaminase 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ADA2 p.His260Tyr Uncertain significance ★ ⚠ 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
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

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-his260gln (accessed [today's date]).

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