Is GART p.Val1007Ala (c.3020T>C) pathogenic?

GART p.Val1007Ala (c.3020T>C) is classified Uncertain significance in GART (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0724); Ultra-rare (popmax 0.032%, afr).

How common is GART p.Val1007Ala (c.3020T>C) in the general population?

GART p.Val1007Ala (c.3020T>C) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about GART p.Val1007Ala (c.3020T>C)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

GART p.Val1007Ala

c.3020T>C · VCV4261970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.00	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 0.083	GERP 2.4
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0042 · regional, not allelic
Overall
CADD	7.391	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 0.032% African / African-American · 24/74,956 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00205% 33/1,611,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,123
Admixed American	0.00672%	14,879
Remaining individualsnot grpmax-eligible	0.00641%	15,595
European (non-Finnish)	8.49e-05%	1,178,514

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.Val1007Ala
Coding: c.3020T>C
MANE Select: NM_000819
Type: single nucleotide variant
Location: chr21:33504137 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 40 PDB
Residue 1007: an α-helix; the 'gart domain' region

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-val1007ala (accessed [today's date]).

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