Is ADA p.Ile27Val (c.79A>G) pathogenic?

ADA p.Ile27Val (c.79A>G) is classified Uncertain significance in ADA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-24). AlphaMissense: likely benign (0.1748); Very rare (popmax 0.00336%, amr); Associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency.

How common is ADA p.Ile27Val (c.79A>G) in the general population?

ADA p.Ile27Val (c.79A>G) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about ADA p.Ile27Val (c.79A>G)?

AlphaMissense predicts likely benign (score 0.1748) — an in-silico prediction, not a clinical call.

ADA p.Ile27Val

Q: What condition is associated with ADA p.Ile27Val (c.79A>G)?

ADA p.Ile27Val (c.79A>G) is associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (ClinVar).

Q: How is Severe combined immunodeficiency due to adenosine deaminase deficiency inherited?

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

c.79A>G · VCV3625899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1748	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.00336% Admixed American · 2/59,512 alleles

Filtering AF 0.000557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000248% 4/1,610,482 alleles · very rare exomes 3/1,458,526 · genomes 1/151,956 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00336%	29,756
Remaining individualsnot grpmax-eligible	0.0016%	62,378
European (non-Finnish)	8.49e-05%	1,178,412

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.Ile27Val
Coding: c.79A>G
MANE Select: NM_000022
Type: single nucleotide variant
Location: chr20:44636243 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 27: an α-helix

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

Disease context

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to adenosine deaminase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

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-ile27val (accessed [today's date]).

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