Is OAT p.Pro202Leu (c.605C>T) pathogenic?

OAT p.Pro202Leu (c.605C>T) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.2278); Ultra-rare (popmax 0.0165%, mid); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Pro202Leu (c.605C>T)?

OAT p.Pro202Leu (c.605C>T) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Pro202Leu (c.605C>T) in the general population?

OAT p.Pro202Leu (c.605C>T) is ultra-rare (popmax 0.0165%, 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.Pro202Leu (c.605C>T)?

AlphaMissense predicts likely benign (score 0.2278) — an in-silico prediction, not a clinical call.

OAT p.Pro202Leu

c.605C>T · rs776703980 · VCV2166017

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2278 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.2278	likely benign
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -13.51	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.012% 193/1,614,066 alleles · ultra-rare exomes 182/1,461,818 · genomes 11/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0266%	3,766
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0134%	7,468
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
African / African-American	0.00533%	18,751
Admixed American	0.005%	20,000

Finnish 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.Pro202Leu
Coding: c.605C>T
MANE Select: NM_000274
dbSNP: rs776703980
Type: single nucleotide variant
Location: chr10:124405479 (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

For Gyrate atrophy of choroid and retina (Orphanet):

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

Similar variants

OAT p.Pro202Ser Uncertain significance ★★ ⚠ same residue
OAT p.Pro202Thr Uncertain significance ★ ⚠ same residue
OAT p.Pro202= 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

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-pro202leu (accessed [today's date]).

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