Is ADA2 p.Thr317= (c.951G>A) pathogenic?

ADA2 p.Thr317= (c.951G>A) is classified Likely benign in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). Ultra-rare (popmax 0.0165%, mid); Associated with deficiency of adenosine deaminase 2.

What condition is associated with ADA2 p.Thr317= (c.951G>A)?

ADA2 p.Thr317= (c.951G>A) is associated with deficiency of adenosine deaminase 2 (ClinVar).

How common is ADA2 p.Thr317= (c.951G>A) in the general population?

ADA2 p.Thr317= (c.951G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Deficiency of adenosine deaminase 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ADA2 p.Thr317=

c.951G>A · rs752600591 · VCV2745742

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

deficiency of adenosine deaminase 2

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 -0.87	GERP -2.4
Overall
CADD	6.437	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00144% 21/1,461,446 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.00549%	18,216
African / African-American	0.004%	25,014
Admixed American	0.00333%	30,005
Finnishnot grpmax-eligible	0.00312%	32,020
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000593%	168,520

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.Thr317=
Coding: c.951G>A
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs752600591
Type: single nucleotide variant
Location: chr22:17189963 (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.Thr317Met Uncertain significance ★★ ⚠ same residue
TADA2A p.Arg317His 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

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-thr317 (accessed [today's date]).

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