Is OAT p.Arg331Leu (c.992G>T) pathogenic?

OAT p.Arg331Leu (c.992G>T) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1934); Very rare (popmax 0.000679%, nfe); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Arg331Leu (c.992G>T)?

OAT p.Arg331Leu (c.992G>T) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Arg331Leu (c.992G>T) in the general population?

OAT p.Arg331Leu (c.992G>T) is very rare (popmax 0.000679%, nfe) (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.Arg331Leu (c.992G>T)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

OAT p.Arg331Leu

c.992G>T · rs201504751 · VCV1501254

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.76	pathogenic-leaning
SaProt	LLR -12.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	26.5	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 0.000679% European (non-Finnish) · 8/1,178,966 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,612,140 alleles · very rare exomes 8/1,459,990 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,418
European (non-Finnish)grpmax	0.000679%	147,371

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg331Leu
Coding: c.992G>T
MANE Select: NM_000274
dbSNP: rs201504751
Type: single nucleotide variant
Location: chr10:124401748 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 331: 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.Arg331Ter Pathogenic ★★ same residue
OAT p.Arg331Gln Uncertain significance ★ ⚠ same residue
OAT p.Arg331fs Pathogenic ★ 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

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-arg331leu (accessed [today's date]).

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