Is OAT p.Val258Asp (c.773T>A) pathogenic?

OAT p.Val258Asp (c.773T>A) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.9621); Very rare (popmax 0.00771%, nfe); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Val258Asp (c.773T>A)?

OAT p.Val258Asp (c.773T>A) is associated with Inborn genetic diseases, ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Val258Asp (c.773T>A) in the general population?

OAT p.Val258Asp (c.773T>A) is very rare (popmax 0.00771%, nfe) (gnomAD).

What do computational predictors say about OAT p.Val258Asp (c.773T>A)?

AlphaMissense predicts likely pathogenic (score 0.9621) — an in-silico prediction, not a clinical call.

OAT p.Val258Asp

c.773T>A · rs746547714 · VCV2044543

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00771%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9621	likely pathogenic
REVEL	0.962	strongly pathogenic-leaning
SaProt	LLR -14.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.79, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00771% European (non-Finnish) · 91/1,180,018 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00592%

Overall 0.00582% 94/1,613,834 alleles · very rare exomes 88/1,461,642 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00771%	12,967
African / African-American	0.004%	24,977

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.Val258Asp
Coding: c.773T>A
MANE Select: NM_000274
dbSNP: rs746547714
Type: single nucleotide variant
Location: chr10:124403054 (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

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

Also linked: ornithine aminotransferase deficiency

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-val258asp (accessed [today's date]).

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