Is OAT p.Ile432Phe (c.1294A>T) pathogenic?

OAT p.Ile432Phe (c.1294A>T) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-11). AlphaMissense: ambiguous (0.455); Absent from gnomAD v4.1; Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Ile432Phe (c.1294A>T)?

OAT p.Ile432Phe (c.1294A>T) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Ile432Phe (c.1294A>T) in the general population?

OAT p.Ile432Phe (c.1294A>T) is absent from gnomAD v4.1 (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.Ile432Phe (c.1294A>T)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

OAT p.Ile432Phe

c.1294A>T · rs2494426916 · VCV2109249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.849	moderately pathogenic-leaning
SaProt	LLR -10.20	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	27.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OAT
Protein: p.Ile432Phe
Coding: c.1294A>T
MANE Select: NM_000274
dbSNP: rs2494426916
Type: single nucleotide variant
Location: chr10:124397968 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 432: 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 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
OAT p.Arg180Thr 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-ile432phe (accessed [today's date]).

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