Is DAO p.Val164Leu (c.490G>T) pathogenic?

DAO p.Val164Leu (c.490G>T) is classified Likely benign in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-31). AlphaMissense: ambiguous (0.3507); Very rare (popmax 8.47e-05%, nfe).

How common is DAO p.Val164Leu (c.490G>T) in the general population?

DAO p.Val164Leu (c.490G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DAO p.Val164Leu (c.490G>T)?

AlphaMissense predicts ambiguous (score 0.3507) — an in-silico prediction, not a clinical call.

DAO p.Val164Leu

c.490G>T · rs1451688633 · VCV873280

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3507 · ACMG-weighted

gnomAD v4.1

Rare

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

Computational evidence

Protein change
AlphaMissense	0.3507	ambiguous
REVEL	0.508	indeterminate
SaProt	LLR -7.41	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	21.7	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) · 1/1,179,976 alleles

Overall 0.000657% 1/152,164 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: DAO
Protein: p.Val164Leu
Coding: c.490G>T
MANE Select: NM_001917
dbSNP: rs1451688633
Type: single nucleotide variant
Location: chr12:108893019 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 164: a binding site

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

Similar variants

DAO p.Ile318Ser Uncertain significance ★★ ⚠ same type
DAO c.195-99C>T Benign ★★ same type
DAO c.387-258A>G Benign ★★ same type
DAO c.453-182G>C Benign ★★ same type
DAO c.507+98G>A Benign ★★ same type
DAO c.508-55A>G Benign ★★ same type
DAO c.696-25C>T Benign ★★ same type
DAO c.912+166C>T Benign ★★ 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/dao-p-val164leu (accessed [today's date]).

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