Is GART p.Ile45Phe (c.133A>T) pathogenic?

GART p.Ile45Phe (c.133A>T) is classified Uncertain significance in GART (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: likely benign (0.2004); Absent from gnomAD v4.1.

How common is GART p.Ile45Phe (c.133A>T) in the general population?

GART p.Ile45Phe (c.133A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GART p.Ile45Phe (c.133A>T)?

AlphaMissense predicts likely benign (score 0.2004) — an in-silico prediction, not a clinical call.

GART p.Ile45Phe

c.133A>T · rs2517269113 · VCV3098600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2004 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2004	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 4.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0042 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GART
Protein: p.Ile45Phe
Coding: c.133A>T
MANE Select: NM_000819
dbSNP: rs2517269113
Type: single nucleotide variant
Location: chr21:33539183 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 40 PDB
Residue 45: a β-strand

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

Similar variants

GART p.Ala122Thr Uncertain significance ★ ⚠ same type
GART p.Ala133Val Uncertain significance ★ ⚠ same type
GART p.Ala154Ser Uncertain significance ★ ⚠ same type
GART p.Ala550Thr Uncertain significance ★ ⚠ same type
GART p.Ala550Val Uncertain significance ★ ⚠ same type
GART p.Ala589Val Uncertain significance ★ ⚠ same type
GART p.Ala728Pro Uncertain significance ★ ⚠ same type
GART p.Ala846Thr Uncertain significance ★ ⚠ 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/gart-p-ile45phe (accessed [today's date]).

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