Is OAT p.Ile185Val (c.553A>G) pathogenic?

OAT p.Ile185Val (c.553A>G) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-10). AlphaMissense: likely benign (0.0666); Ultra-rare (popmax 0.033%, mid).

How common is OAT p.Ile185Val (c.553A>G) in the general population?

OAT p.Ile185Val (c.553A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about OAT p.Ile185Val (c.553A>G)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

OAT p.Ile185Val

c.553A>G · VCV4909889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP 0.89, phastCons 0.018
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	14.72	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00062% 10/1,614,088 alleles · ultra-rare exomes 10/1,461,820 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0011%	91,080
European (non-Finnish)	0.000593%	168,569

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.Ile185Val
Coding: c.553A>G
MANE Select: NM_000274
Type: single nucleotide variant
Location: chr10:124405531 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 185: an α-helix

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

Similar variants

OAT c.1014+1G>A Likely pathogenic ★★ same type
OAT c.199+2T>A Likely pathogenic ★★ same type
OAT c.425-2A>G Pathogenic ★★ same type
OAT c.520+1G>A Likely pathogenic ★★ same type
OAT c.648+1G>A Likely pathogenic ★★ same type
OAT c.772-1G>A Pathogenic/Likely pathogenic ★★ same type
OAT c.900+1G>A Pathogenic/Likely pathogenic ★★ same type
OAT p.Arg180Thr Pathogenic/Likely pathogenic ★★ same type

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-ile185val (accessed [today's date]).

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