Is GARS1 p.Arg464fs (c.1391_1407del) pathogenic?

GARS1 p.Arg464fs (c.13911407del) is classified Uncertain significance in GARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-26). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with GARS1 p.Arg464fs (c.1391_1407del)?

GARS1 p.Arg464fs (c.1391_1407del) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Arg464fs (c.1391_1407del) in the general population?

GARS1 p.Arg464fs (c.1391_1407del) is absent from gnomAD (gnomAD).

GARS1 p.Arg464fs

c.1391_1407del · rs2128135088 · VCV1680935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GARS1
Protein: p.Arg464fs
Coding: c.1391_1407del
MANE Select: NM_002047
dbSNP: rs2128135088
Type: Deletion
Location: chr7:30621422 (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.Arg722fs Uncertain significance ★★ same condition
GARS1 c.1031+9del Likely benign ★★ same condition
GARS1 c.1699+23_1699+26del Likely benign ★★ same condition
GARS1 c.1904-19del Likely benign ★★ same condition
GARS1 c.659-3del Uncertain significance ★ same condition
GARS1 p.Glu597del Uncertain significance ★ same condition
GARS1 p.Lys264del Uncertain significance ★ same condition
GARS1 p.Met692fs Uncertain significance ★ 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-arg464fs (accessed [today's date]).

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