Is DAO p.Pro103= (c.309G>A) pathogenic?

DAO p.Pro103= (c.309G>A) is classified Uncertain significance in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). Ultra-rare (popmax 0.0111%, nfe); Associated with DAO-related disorder.

What condition is associated with DAO p.Pro103= (c.309G>A)?

DAO p.Pro103= (c.309G>A) is associated with DAO-related disorder (ClinVar).

How common is DAO p.Pro103= (c.309G>A) in the general population?

DAO p.Pro103= (c.309G>A) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

DAO p.Pro103=

c.309G>A · rs147144733 · VCV2634811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Conditions

DAO-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.75	donor loss · deltas
Pangolin	Δ0.57	loss · gain 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.9	GERP 0.3, phastCons 1
Overall
CADD	18.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% European (non-Finnish) · 131/1,174,974 alleles

Filtering AF 0.00956% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.00877% 141/1,608,404 alleles · ultra-rare exomes 134/1,456,298 · genomes 7/152,106 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,902
European (non-Finnish)grpmax	0.0111%	8,969
Admixed American	0.00167%	59,990
African / African-American	0.00134%	74,740
South Asian	0.0011%	90,970

Remaining individuals 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.Pro103=
Coding: c.309G>A
MANE Select: NM_001917
dbSNP: rs147144733
Type: single nucleotide variant
Location: chr12:108887564 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 103: an α-helix

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

Disease context

DAO-related disorder

Similar variants

DAO p.Pro103Leu 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.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-pro103 (accessed [today's date]).

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