Is OAT p.Ala415Val (c.1244C>T) pathogenic?

OAT p.Ala415Val (c.1244C>T) is classified Uncertain significance in OAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely pathogenic (0.6144); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Ala415Val (c.1244C>T)?

OAT p.Ala415Val (c.1244C>T) is associated with Inborn genetic diseases (ClinVar).

How common is OAT p.Ala415Val (c.1244C>T) in the general population?

OAT p.Ala415Val (c.1244C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about OAT p.Ala415Val (c.1244C>T)?

AlphaMissense predicts likely pathogenic (score 0.6144) — an in-silico prediction, not a clinical call.

OAT p.Ala415Val

c.1244C>T · VCV3923391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6144 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6144	likely pathogenic
REVEL	0.745	pathogenic-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.46	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.6	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	27.3	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,613,858 alleles · ultra-rare exomes 17/1,461,732 · genomes 2/152,126 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-American	0.00134%	74,892
European (non-Finnish)	0.00119%	84,281
South Asian	0.0011%	91,086

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.Ala415Val
Coding: c.1244C>T
MANE Select: NM_000274
Type: single nucleotide variant
Location: chr10:124398018 (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

Similar variants

OAT p.Ala415= Conflicting classifications of pathogenicity ★ 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-ala415val (accessed [today's date]).

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