Is DAO p.Ser345Phe (c.1034C>T) pathogenic?

DAO p.Ser345Phe (c.1034C>T) is classified Uncertain significance in DAO (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-01). AlphaMissense: likely benign (0.1249); Ultra-rare (popmax 0.0358%, nfe).

How common is DAO p.Ser345Phe (c.1034C>T) in the general population?

DAO p.Ser345Phe (c.1034C>T) is ultra-rare (popmax 0.0358%, nfe) (gnomAD).

What do computational predictors say about DAO p.Ser345Phe (c.1034C>T)?

AlphaMissense predicts likely benign (score 0.1249) — an in-silico prediction, not a clinical call.

DAO p.Ser345Phe

c.1034C>T · rs143732132 · VCV2672518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1249 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0358%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1249	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.87 · regional, not allelic
Overall
CADD	25.3	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 0.0358% European (non-Finnish) · 422/1,179,934 alleles

Filtering AF 0.0329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0318%

Overall 0.0275% 444/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0358%	2,796
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Finnishnot grpmax-eligible	0.0109%	9,141
African / African-American	0.00533%	18,760

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.Ser345Phe
Coding: c.1034C>T
MANE Select: NM_001917
dbSNP: rs143732132
Type: single nucleotide variant
Location: chr12:108900525 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.26 · 22 PDB

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-ser345phe (accessed [today's date]).

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