Is OAT p.Glu359Val (c.1076A>T) pathogenic?

OAT p.Glu359Val (c.1076A>T) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: ambiguous (0.4495); Very rare (popmax 0.0088%, sas); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Glu359Val (c.1076A>T)?

OAT p.Glu359Val (c.1076A>T) is associated with Inborn genetic diseases (ClinVar).

How common is OAT p.Glu359Val (c.1076A>T) in the general population?

OAT p.Glu359Val (c.1076A>T) is very rare (popmax 0.0088%, sas) (gnomAD).

What do computational predictors say about OAT p.Glu359Val (c.1076A>T)?

AlphaMissense predicts ambiguous (score 0.4495) — an in-silico prediction, not a clinical call.

OAT p.Glu359Val

c.1076A>T · VCV3923390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0088%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4495	ambiguous
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -16.14	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	24.8	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 0.0088% South Asian · 8/90,920 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.000497% 8/1,609,956 alleles · very rare exomes 7/1,457,736 · genomes 1/152,220 · joint denominator

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.Glu359Val
Coding: c.1076A>T
MANE Select: NM_000274
Type: single nucleotide variant
Location: chr10:124400923 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 359: 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

Similar variants

OAT p.Glu359Gly Uncertain significance ★ ⚠ same residue
OAT p.Glu359= Likely benign ★ same residue
OAT p.Ala379Thr Uncertain significance ★★ ⚠ same condition
OAT p.Arg16His Uncertain significance ★★ ⚠ same condition
OAT p.Asn118Tyr Uncertain significance ★★ ⚠ same condition
OAT p.Asp205Asn Uncertain significance ★★ ⚠ same condition
OAT p.Asp205Gly Uncertain significance ★★ ⚠ same condition
OAT p.Asp263Val Uncertain significance ★★ ⚠ 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-glu359val (accessed [today's date]).

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