Is ADA2 p.Ile480Val (c.1438A>G) pathogenic?

ADA2 p.Ile480Val (c.1438A>G) is classified Uncertain significance in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). AlphaMissense: likely benign (0.104); Very rare (popmax 0.00534%, afr).

How common is ADA2 p.Ile480Val (c.1438A>G) in the general population?

ADA2 p.Ile480Val (c.1438A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ADA2 p.Ile480Val (c.1438A>G)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

ADA2 p.Ile480Val

c.1438A>G · VCV4689012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -6.92	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 0.14	GERP 0.29, phastCons 0.068
Overall
CADD	18.83	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 0.00534% African / African-American · 4/74,902 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/152,186 alleles · very rare

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.Ile480Val
Coding: c.1438A>G
MANE Select: NM_001166105 · reported on NM_001282225
Type: single nucleotide variant
Location: chr22:17181824 (GRCh38)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

Full ADA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADA2 p.Ile480Thr Uncertain significance ★ ⚠ same residue
ADA2 c.754-2A>G Likely pathogenic ★★ same type
ADA2 c.882-2A>G Pathogenic ★★ same type
ADA2 c.973-2A>G Pathogenic ★★ same type
ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same type
ADA2 p.Arg169Trp Pathogenic/Likely pathogenic ★★ same type
ADA2 p.Arg306Ter Likely pathogenic ★★ same type
ADA2 p.Arg312Ter Pathogenic ★★ same type

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-ile480val (accessed [today's date]).

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