Is GART p.Arg13Thr (c.38G>C) pathogenic?

GART p.Arg13Thr (c.38G>C) is classified Uncertain significance in GART (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.9132); Very rare (popmax 0.00822%, nfe).

How common is GART p.Arg13Thr (c.38G>C) in the general population?

GART p.Arg13Thr (c.38G>C) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about GART p.Arg13Thr (c.38G>C)?

AlphaMissense predicts likely pathogenic (score 0.9132) — an in-silico prediction, not a clinical call.

GART p.Arg13Thr

c.38G>C · VCV3518869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9132	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -14.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0042 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00822% European (non-Finnish) · 97/1,179,988 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00626% 101/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,165
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: GART
Protein: p.Arg13Thr
Coding: c.38G>C
MANE Select: NM_000819
Type: single nucleotide variant
Location: chr21:33539278 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 40 PDB
Residue 13: an α-helix

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-arg13thr (accessed [today's date]).

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