Is DAO p.Arg199Gln (c.596G>A) pathogenic?

DAO p.Arg199Gln (c.596G>A) is classified Likely benign in DAO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-09). AlphaMissense: ambiguous (0.3787); Rare (popmax 0.214%, sas); Associated with DAO-related disorder.

What condition is associated with DAO p.Arg199Gln (c.596G>A)?

DAO p.Arg199Gln (c.596G>A) is associated with DAO-related disorder (ClinVar).

How common is DAO p.Arg199Gln (c.596G>A) in the general population?

DAO p.Arg199Gln (c.596G>A) is rare (popmax 0.214%, sas) (gnomAD).

What do computational predictors say about DAO p.Arg199Gln (c.596G>A)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

DAO p.Arg199Gln

c.596G>A · rs200850756 · VCV3045347

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DAO-related disorder

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.679	pathogenic-leaning
SaProt	LLR -15.56	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	34.0	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 0.214% South Asian · 195/91,004 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.0338% 546/1,613,112 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.214%	467
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
Remaining individualsnot grpmax-eligible	0.0737%	1,358
European (non-Finnish)	0.0198%	5,061
African / African-American	0.0107%	9,375
Admixed American	0.00834%	11,991
Finnishnot grpmax-eligible	0.00156%	63,964

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.Arg199Gln
Coding: c.596G>A
MANE Select: NM_001917
dbSNP: rs200850756
Type: single nucleotide variant
Location: chr12:108894351 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 199: a UniProt-annotated variant site (found in a patient with als; impairs fad binding; over 200-fold decreased affinity for d-serine; 1800-fold decreased affinity for d-alanine); a UniProt-annotated variant site (found in a patient with als; decreased function in d-serine catabolic process; 3- to 4-fold decrease in vmax with d-serine, d-alanine and d-proline as substrates; impairs fad binding; decreased affinity for d-serine, d-alanine and d-proline; leads to tetramerization of the holoenzyme; leads to the formation of ubiquitinated protein aggregates; promotes induction of apoptosis; causes cell death in motor neurons in a manner at least partially dependent on the n-methyl-d-aspartic acid receptor); 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.Arg199Trp Likely benign ⚠ same residue
DAO p.Arg290Gln Uncertain significance ★ ⚠ same condition
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

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-arg199gln (accessed [today's date]).

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