Is OAT p.Glu424Asp (c.1272G>T) pathogenic?

OAT p.Glu424Asp (c.1272G>T) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.3072); Very rare (popmax 0.00167%, amr); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Glu424Asp (c.1272G>T)?

OAT p.Glu424Asp (c.1272G>T) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Glu424Asp (c.1272G>T) in the general population?

OAT p.Glu424Asp (c.1272G>T) is very rare (popmax 0.00167%, amr) (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.Glu424Asp (c.1272G>T)?

AlphaMissense predicts likely benign (score 0.3072) — an in-silico prediction, not a clinical call.

OAT p.Glu424Asp

c.1272G>T · rs1170702129 · VCV1496148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.3072	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -0.14, phastCons 0.021
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00167% Admixed American · 1/60,018 alleles

Overall 6.2e-05% 1/1,613,962 alleles · very rare exomes 1/1,461,654 · genomes 0/152,308 · 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.Glu424Asp
Coding: c.1272G>T
MANE Select: NM_000274
dbSNP: rs1170702129
Type: single nucleotide variant
Location: chr10:124397990 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 424: 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-glu424asp (accessed [today's date]).

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