Is DAO p.Phe90Val (c.268T>G) pathogenic?

DAO p.Phe90Val (c.268T>G) is classified Likely benign in DAO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-16). AlphaMissense: likely benign (0.2732); Ultra-rare (popmax 0.0383%, amr); Associated with DAO-related disorder.

What condition is associated with DAO p.Phe90Val (c.268T>G)?

DAO p.Phe90Val (c.268T>G) is associated with DAO-related disorder (ClinVar).

How common is DAO p.Phe90Val (c.268T>G) in the general population?

DAO p.Phe90Val (c.268T>G) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about DAO p.Phe90Val (c.268T>G)?

AlphaMissense predicts likely benign (score 0.2732) — an in-silico prediction, not a clinical call.

DAO p.Phe90Val

c.268T>G · rs146917361 · VCV3035857

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DAO-related disorder

Computational evidence

Protein change
AlphaMissense	0.2732	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -9.14	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 1.1	GERP -4.4, phastCons 0.98
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	20.2	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 0.0383% Admixed American · 23/59,982 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0242% 390/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.125%	800
Finnishnot grpmax-eligible	0.0515%	1,940
Admixed Americangrpmax	0.0383%	2,608
Remaining individualsnot grpmax-eligible	0.0352%	2,840
European (non-Finnish)	0.0223%	4,487
South Asian	0.00988%	10,120
African / African-American	0.004%	24,971

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe90Val
Coding: c.268T>G
MANE Select: NM_001917
dbSNP: rs146917361
Type: single nucleotide variant
Location: chr12:108887523 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 90: 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.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
DAO p.Arg286Cys 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-phe90val (accessed [today's date]).

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