Is OAT p.Lys135Arg (c.404A>G) pathogenic?

OAT p.Lys135Arg (c.404A>G) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.0901); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Lys135Arg (c.404A>G)?

OAT p.Lys135Arg (c.404A>G) is associated with Inborn genetic diseases (ClinVar).

How common is OAT p.Lys135Arg (c.404A>G) in the general population?

OAT p.Lys135Arg (c.404A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about OAT p.Lys135Arg (c.404A>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

OAT p.Lys135Arg

c.404A>G · VCV3882181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00134% African / African-American · 1/74,782 alleles

Overall 0.000124% 2/1,608,944 alleles · very rare exomes 1/1,456,862 · genomes 1/152,082 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,782
European (non-Finnish)	8.5e-05%	1,176,512

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.Lys135Arg
Coding: c.404A>G
MANE Select: NM_000274
Type: single nucleotide variant
Location: chr10:124408761 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 135: a β-strand

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.Lys135Asn Uncertain significance ★ ⚠ 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
OAT p.Asp410Asn 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-lys135arg (accessed [today's date]).

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