Is ADA2 p.Val203Gly (c.608T>G) pathogenic?

ADA2 p.Val203Gly (c.608T>G) is classified Uncertain significance in ADA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely benign (0.3217); Very rare (popmax 8.47e-05%, nfe).

How common is ADA2 p.Val203Gly (c.608T>G) in the general population?

ADA2 p.Val203Gly (c.608T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ADA2 p.Val203Gly (c.608T>G)?

AlphaMissense predicts likely benign (score 0.3217) — an in-silico prediction, not a clinical call.

ADA2 p.Val203Gly

c.608T>G · rs1340031421 · VCV2672892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3217	likely benign
REVEL	0.548	indeterminate
SaProt	LLR -12.43	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.89, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.84e-05% 1/1,461,840 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.Val203Gly
Coding: c.608T>G
MANE Select: NM_001166105 · reported on NM_001282225
dbSNP: rs1340031421
Type: single nucleotide variant
Location: chr22:17203708 (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.Val203Ala 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-val203gly (accessed [today's date]).

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