Is OAT p.Pro95Ser (c.283C>T) pathogenic?

OAT p.Pro95Ser (c.283C>T) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-12). AlphaMissense: likely benign (0.2366); Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Pro95Ser (c.283C>T)?

OAT p.Pro95Ser (c.283C>T) is associated with Inborn genetic diseases, ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Pro95Ser (c.283C>T) in the general population?

OAT p.Pro95Ser (c.283C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about OAT p.Pro95Ser (c.283C>T)?

AlphaMissense predicts likely benign (score 0.2366) — an in-silico prediction, not a clinical call.

OAT p.Pro95Ser

c.283C>T · rs372105047 · VCV864129

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2366 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2366	likely benign
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -11.76	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	28.4	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 0.0174% African / African-American · 13/74,850 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00093% 15/1,613,468 alleles · ultra-rare exomes 5/1,461,434 · genomes 10/152,034 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,758
European (non-Finnish)	0.000169%	589,977

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.Pro95Ser
Coding: c.283C>T
MANE Select: NM_000274
dbSNP: rs372105047
Type: single nucleotide variant
Location: chr10:124408882 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 95: an α-helix

Full OAT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ornithine aminotransferase deficiency

Similar variants

OAT p.Pro95= 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
OAT c.900+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-pro95ser (accessed [today's date]).

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