Is OAT p.Arg16Cys (c.46C>T) pathogenic?

OAT p.Arg16Cys (c.46C>T) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-27). AlphaMissense: likely benign (0.1312); Ultra-rare (popmax 0.0658%, mid); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Arg16Cys (c.46C>T)?

OAT p.Arg16Cys (c.46C>T) is associated with ornithine aminotransferase deficiency, inherited retinal dystrophy (ClinVar).

How common is OAT p.Arg16Cys (c.46C>T) in the general population?

OAT p.Arg16Cys (c.46C>T) is ultra-rare (popmax 0.0658%, mid) (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.Arg16Cys (c.46C>T)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

OAT p.Arg16Cys

c.46C>T · rs778757920 · VCV1365342

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.654	pathogenic-leaning
SaProt	LLR -9.82	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.69, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	22.9	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 0.0658% Middle Eastern · 4/6,078 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00291% 47/1,614,028 alleles · ultra-rare exomes 42/1,461,862 · genomes 5/152,166 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0658%	1,520
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.005%	19,997
European (non-Finnish)	0.00288%	34,707
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,088

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.Arg16Cys
Coding: c.46C>T
MANE Select: NM_000274
dbSNP: rs778757920
Type: single nucleotide variant
Location: chr10:124412126 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB

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

Also linked: inherited retinal dystrophy

For Gyrate atrophy of choroid and retina (Orphanet):

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

Similar variants

OAT p.Arg16His Uncertain significance ★★ ⚠ same residue
OAT p.Arg16= Likely benign ★ 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

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-arg16cys (accessed [today's date]).

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