Is DAO p.Pro105Arg (c.314C>G) pathogenic?

DAO p.Pro105Arg (c.314C>G) is classified Uncertain significance in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.5994); Rare (popmax 0.144%, sas); Associated with Inborn genetic diseases.

What condition is associated with DAO p.Pro105Arg (c.314C>G)?

DAO p.Pro105Arg (c.314C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DAO p.Pro105Arg (c.314C>G) in the general population?

DAO p.Pro105Arg (c.314C>G) is rare (popmax 0.144%, sas) (gnomAD).

What do computational predictors say about DAO p.Pro105Arg (c.314C>G)?

AlphaMissense predicts likely pathogenic (score 0.5994) — an in-silico prediction, not a clinical call.

DAO p.Pro105Arg

c.314C>G · rs532474005 · VCV2600891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5994 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5994	likely pathogenic
REVEL	0.69	pathogenic-leaning
SaProt	LLR -14.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	25.1	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 0.144% South Asian · 131/90,992 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00819% 132/1,611,236 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.144%	695
Remaining individualsnot grpmax-eligible	0.0016%	62,336

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.Pro105Arg
Coding: c.314C>G
MANE Select: NM_001917
dbSNP: rs532474005
Type: single nucleotide variant
Location: chr12:108889473 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB
Residue 105: an α-helix

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-pro105arg (accessed [today's date]).

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