Is GART p.Arg775Cys (c.2323C>T) pathogenic?

GART p.Arg775Cys (c.2323C>T) is classified Uncertain significance in GART (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00893%, eas).

How common is GART p.Arg775Cys (c.2323C>T) in the general population?

GART p.Arg775Cys (c.2323C>T) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about GART p.Arg775Cys (c.2323C>T)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

GART p.Arg775Cys

c.2323C>T · rs200269758 · VCV2588937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.28	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0042 · regional, not allelic
Overall
CADD	21.7	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 0.00893% East Asian · 4/44,788 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00174% 28/1,609,428 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,197
African / African-American	0.00402%	24,877
South Asian	0.00333%	30,071
Admixed American	0.00168%	59,426
European (non-Finnish)	0.00144%	69,300

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.Arg775Cys
Coding: c.2323C>T
MANE Select: NM_000819
dbSNP: rs200269758
Type: single nucleotide variant
Location: chr21:33509912 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 40 PDB
Residue 775: the 'airs 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-arg775cys (accessed [today's date]).

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