Is DAO p.Arg290Gln (c.869G>A) pathogenic?

DAO p.Arg290Gln (c.869G>A) is classified Uncertain significance in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: ambiguous (0.5153); Ultra-rare (popmax 0.022%, sas); Associated with DAO-related disorder.

What condition is associated with DAO p.Arg290Gln (c.869G>A)?

DAO p.Arg290Gln (c.869G>A) is associated with DAO-related disorder (ClinVar).

How common is DAO p.Arg290Gln (c.869G>A) in the general population?

DAO p.Arg290Gln (c.869G>A) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about DAO p.Arg290Gln (c.869G>A)?

AlphaMissense predicts ambiguous (score 0.5153) — an in-silico prediction, not a clinical call.

DAO p.Arg290Gln

c.869G>A · rs372560295 · VCV2634586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5153 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DAO-related disorder

Computational evidence

Protein change
AlphaMissense	0.5153	ambiguous
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -14.10	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	31.0	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 0.022% South Asian · 20/91,002 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00229% 37/1,613,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,550
East Asian	0.00891%	11,218
European (non-Finnish)	0.0011%	90,762

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: DAO
Protein: p.Arg290Gln
Coding: c.869G>A
MANE Select: NM_001917
dbSNP: rs372560295
Type: single nucleotide variant
Location: chr12:108899432 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 290: a β-strand

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

Disease context

DAO-related disorder

Similar variants

DAO p.Arg297His Uncertain significance ★ ⚠ same condition
DAO p.Arg2Ser Uncertain significance ★ ⚠ same condition
DAO p.Arg38His Uncertain significance ★ ⚠ same condition
DAO p.Gly131Cys Uncertain significance ★ ⚠ same condition
DAO p.Pro103= Uncertain significance ★ same condition
DAO p.Thr235Ile Uncertain significance ★ ⚠ same condition
DAO p.Arg286Cys Uncertain significance ⚠ same condition
DAO p.Arg38Cys Uncertain significance ⚠ 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/dao-p-arg290gln (accessed [today's date]).

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