Is DAO p.Val34Asp (c.101T>A) pathogenic?

DAO p.Val34Asp (c.101T>A) is classified Uncertain significance in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely pathogenic (0.9699); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with DAO p.Val34Asp (c.101T>A)?

DAO p.Val34Asp (c.101T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DAO p.Val34Asp (c.101T>A) in the general population?

DAO p.Val34Asp (c.101T>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DAO p.Val34Asp (c.101T>A)?

AlphaMissense predicts likely pathogenic (score 0.9699) — an in-silico prediction, not a clinical call.

DAO p.Val34Asp

c.101T>A · VCV3270852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9699 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9699	likely pathogenic · top 2% in DAO
REVEL	0.717	pathogenic-leaning
SaProt	LLR -15.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.01% Admixed American · 6/59,980 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,794 alleles · ultra-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: DAO
Protein: p.Val34Asp
Coding: c.101T>A
MANE Select: NM_001917
Type: single nucleotide variant
Location: chr12:108885107 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 34: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DAO p.Ile318Ser Uncertain significance ★★ ⚠ same condition
DAO p.Ala175Thr Uncertain significance ★ ⚠ same condition
DAO p.Arg115Gln Uncertain significance ★ ⚠ same condition
DAO p.Arg286His Uncertain significance ★ ⚠ same condition
DAO p.Arg297Cys Uncertain significance ★ ⚠ same condition
DAO p.Arg2Cys Uncertain significance ★ ⚠ same condition
DAO p.Asn180Ser Uncertain significance ★ ⚠ same condition
DAO p.Asn246Ser 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-val34asp (accessed [today's date]).

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