Is DAO p.Pro103Leu (c.308C>T) pathogenic?

DAO p.Pro103Leu (c.308C>T) is classified Likely benign in DAO (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1178); Rare (popmax 0.314%, eas).

How common is DAO p.Pro103Leu (c.308C>T) in the general population?

DAO p.Pro103Leu (c.308C>T) is rare (popmax 0.314%, eas) (gnomAD).

What do computational predictors say about DAO p.Pro103Leu (c.308C>T)?

AlphaMissense predicts likely benign (score 0.1178) — an in-silico prediction, not a clinical call.

DAO p.Pro103Leu

c.308C>T · rs200127576 · VCV710573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1178 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.314%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1178	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	24.9	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 0.314% East Asian · 141/44,854 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.256%

Overall 0.0271% 436/1,608,860 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.314%	318
Remaining individualsnot grpmax-eligible	0.0674%	1,484
European (non-Finnish)	0.0203%	4,938
Middle Eastern	0.0165%	6,054
African / African-American	0.00668%	14,973
South Asian	0.0055%	18,193
Admixed American	0.00333%	30,003
Finnishnot grpmax-eligible	0.00312%	32,004

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.Pro103Leu
Coding: c.308C>T
MANE Select: NM_001917
dbSNP: rs200127576
Type: single nucleotide variant
Location: chr12:108887563 (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

Similar variants

DAO p.Pro103= Uncertain significance ★ same residue
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

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-pro103leu (accessed [today's date]).

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