Is GART p.Arg671Cys (c.2011C>T) pathogenic?

GART p.Arg671Cys (c.2011C>T) is classified Uncertain significance in GART (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0949); Very rare (popmax 0.00334%, amr).

How common is GART p.Arg671Cys (c.2011C>T) in the general population?

GART p.Arg671Cys (c.2011C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about GART p.Arg671Cys (c.2011C>T)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

GART p.Arg671Cys

c.2011C>T · VCV4670899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -10.94	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.9	GERP 4.3, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,966 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000806% 13/1,613,192 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,983
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00133%	74,992
European (non-Finnish)	0.000678%	147,407

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.Arg671Cys
Coding: c.2011C>T
MANE Select: NM_000819
Type: single nucleotide variant
Location: chr21:33517085 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 40 PDB
Residue 671: the 'airs domain' region; an α-helix

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

Similar variants

GART p.Arg671His Uncertain significance ★ ⚠ same residue
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

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-arg671cys (accessed [today's date]).

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