Is OAT p.Glu338= (c.1014G>A) pathogenic?

OAT p.Glu338= (c.1014G>A) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-17). Ultra-rare (popmax 0.0176%, sas); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Glu338= (c.1014G>A)?

OAT p.Glu338= (c.1014G>A) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Glu338= (c.1014G>A) in the general population?

OAT p.Glu338= (c.1014G>A) is ultra-rare (popmax 0.0176%, 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.

OAT p.Glu338=

c.1014G>A · rs762633186 · VCV2185672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.63	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/90,944 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.00118% 19/1,606,438 alleles · ultra-rare exomes 19/1,454,192 · genomes 0/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,684
Remaining individualsnot grpmax-eligible	0.00161%	62,272
European (non-Finnish)	0.00017%	586,841

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.Glu338=
Coding: c.1014G>A
MANE Select: NM_000274
dbSNP: rs762633186
Type: single nucleotide variant
Location: chr10:124401726 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 338: 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-glu338 (accessed [today's date]).

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