Is GARS1 p.Arg602= (c.1806A>G) pathogenic?

GARS1 p.Arg602= (c.1806A>G) is classified Likely benign in GARS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-25). Very rare (popmax 0.00167%, amr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with GARS1 p.Arg602= (c.1806A>G)?

GARS1 p.Arg602= (c.1806A>G) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Arg602= (c.1806A>G) in the general population?

GARS1 p.Arg602= (c.1806A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

GARS1 p.Arg602=

c.1806A>G · rs1314425578 · VCV798590

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP 0.94, phastCons 0.71
Overall
CADD	9.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,962 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00025% 4/1,599,746 alleles · very rare exomes 4/1,447,364 · genomes 0/152,382 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,962
Remaining individualsnot grpmax-eligible	0.00161%	61,974
European (non-Finnish)	0.000171%	583,570

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: GARS1
Protein: p.Arg602=
Coding: c.1806A>G
MANE Select: NM_002047
dbSNP: rs1314425578
Type: single nucleotide variant
Location: chr7:30628666 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB

Full GARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GARS1 p.Arg602Lys Uncertain significance ★ ⚠ same residue
GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.His472Arg Pathogenic ★★ same condition
GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Ile334Phe Pathogenic ★★ same condition
GARS1 p.Ile334Thr Pathogenic/Likely pathogenic ★★ same condition

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/gars1-p-arg602 (accessed [today's date]).

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