Is OAT p.Ala349Pro (c.1045G>C) pathogenic?

OAT p.Ala349Pro (c.1045G>C) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.9896); Very rare (popmax 0.0011%, sas); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Ala349Pro (c.1045G>C)?

OAT p.Ala349Pro (c.1045G>C) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Ala349Pro (c.1045G>C) in the general population?

OAT p.Ala349Pro (c.1045G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Gyrate atrophy of choroid and retina inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OAT p.Ala349Pro (c.1045G>C)?

AlphaMissense predicts likely pathogenic (score 0.9896) — an in-silico prediction, not a clinical call.

OAT p.Ala349Pro

c.1045G>C · VCV4807420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.9896	likely pathogenic · top 3% in OAT
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -15.63	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 3.9	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	26.4	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 0.0011% South Asian · 1/90,934 alleles

Overall 6.21e-05% 1/1,611,258 alleles · very rare exomes 1/1,459,064 · genomes 0/152,194 · joint denominator

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: OAT
Protein: p.Ala349Pro
Coding: c.1045G>C
MANE Select: NM_000274
Type: single nucleotide variant
Location: chr10:124400954 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 349: an α-helix

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

Disease context

ornithine aminotransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gyrate atrophy of choroid and retina (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

OAT p.Ala349Glu Uncertain significance ★ ⚠ same residue
OAT c.1014+1G>A Likely pathogenic ★★ same condition
OAT c.199+2T>A Likely pathogenic ★★ same condition
OAT c.425-2A>G Pathogenic ★★ same condition
OAT c.520+1G>A Likely pathogenic ★★ same condition
OAT c.648+1G>A Likely pathogenic ★★ same condition
OAT c.772-1G>A Pathogenic/Likely pathogenic ★★ same condition
OAT c.900+1G>A Pathogenic/Likely pathogenic ★★ 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/oat-p-ala349pro (accessed [today's date]).

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