Is ADA2 p.Lys267Gln (c.799A>C) pathogenic?

ADA2 p.Lys267Gln (c.799A>C) is classified Uncertain significance in ADA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-17). AlphaMissense: likely benign (0.0883); Absent from gnomAD v4.1; Associated with Deficiency of ADA2.

What condition is associated with ADA2 p.Lys267Gln (c.799A>C)?

ADA2 p.Lys267Gln (c.799A>C) is associated with Deficiency of ADA2 (ClinVar).

How common is ADA2 p.Lys267Gln (c.799A>C) in the general population?

ADA2 p.Lys267Gln (c.799A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADA2 p.Lys267Gln (c.799A>C)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

ADA2 p.Lys267Gln

c.799A>C · rs1601436115 · VCV872927

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Deficiency of ADA2

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.61	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 0.29	GERP -2.1, phastCons 0.18
Overall
CADD	16.47	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.Lys267Gln
Coding: c.799A>C
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs1601436115
Type: single nucleotide variant
Location: chr22:17191765 (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 ADA2

Similar variants

ADA2 p.Arg306Ter Likely pathogenic ★★ same condition
ADA2 p.Gly47Ala Pathogenic ★★ ⚠ same condition
ADA2 p.Gly47Val Pathogenic/Likely pathogenic ★★ same condition
ADA2 p.Thr360Ala Pathogenic ★★ ⚠ same condition
ADA2 p.Ile462Thr Uncertain significance ★★ ⚠ same condition
ADA2 p.Thr492Ala Uncertain significance ★★ ⚠ same condition
ADA2 p.Tyr130Ter Likely pathogenic ★ same condition
ADA2 p.Ala357Thr Conflicting classifications of pathogenicity ★ ⚠ 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-lys267gln (accessed [today's date]).

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