Is ADA p.Val130= (c.390G>A) pathogenic?

ADA p.Val130= (c.390G>A) is classified Benign in ADA (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele; Associated with severe combined immunodeficiency.

ADA p.Val130=

Q: What condition is associated with ADA p.Val130= (c.390G>A)?

ADA p.Val130= (c.390G>A) is associated with severe combined immunodeficiency, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (ClinVar).

Q: How common is ADA p.Val130= (c.390G>A) in the general population?

ADA p.Val130= (c.390G>A) is common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.390G>A · rs61737144 · VCV35653

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

severe combined immunodeficiency

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 0.01	GERP -2.5, phastCons 0.001
Overall
CADD	6.813	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.86% African / African-American · 4,349/74,158 alleles

Filtering AF 5.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.66%

Overall 3.43% 53,864/1,570,220 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.86%	17
Finnishnot grpmax-eligible	4.33%	23
Ashkenazi Jewishnot grpmax-eligible	4.17%	24
Remaining individualsnot grpmax-eligible	3.6%	28
European (non-Finnish)	3.52%	28
Middle Eastern	3.12%	32
Admixed American	2.13%	47
South Asian	1.69%	59
Amishnot grpmax-eligible	1.21%	83
East Asian	0.0117%	8,556

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: ADA
Protein: p.Val130=
Coding: c.390G>A
MANE Select: NM_000022
dbSNP: rs61737144
Type: single nucleotide variant
Location: chr20:44625657 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 130: the 'required for binding to ddp4' region; an α-helix

Full ADA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Similar variants

ADA c.1078+2T>A Likely pathogenic ★★★ same condition
ADA c.219-2A>G Likely pathogenic ★★★ same condition
ADA c.363-2A>G Likely pathogenic ★★★ same condition
ADA c.606+1G>T Likely pathogenic ★★★ same condition
ADA c.975+1G>A Pathogenic ★★★ same condition
ADA c.976-1G>C Pathogenic ★★★ same condition
ADA p.Ala329Val Pathogenic ★★★ same condition
ADA p.Arg149Trp 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/ada-p-val130 (accessed [today's date]).

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