Is AARS1 p.Gln381Ter (c.1140_1141delinsAT) pathogenic?

AARS1 p.Gln381Ter (c.11401141delinsAT) is classified Pathogenic in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-19). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Gln381Ter (c.1140_1141delinsAT)?

AARS1 p.Gln381Ter (c.1140_1141delinsAT) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Gln381Ter (c.1140_1141delinsAT) in the general population?

AARS1 p.Gln381Ter (c.1140_1141delinsAT) is absent from gnomAD (gnomAD).

AARS1 p.Gln381Ter

c.1140_1141delinsAT · rs2507012689 · VCV2865947

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, 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: AARS1
Protein: p.Gln381Ter
Coding: c.1140_1141delinsAT
MANE Select: NM_001605
dbSNP: rs2507012689
Type: Indel
Location: chr16:70267740 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 381: an α-helix

Full AARS1 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

AARS1 p.Gln381= Likely benign ★ same residue
AARS1 c.1222+5_1222+7delinsTTTTTGC Uncertain significance ★★ same condition
AARS1 c.672-565_760delinsCATAGTTGTCAT Likely pathogenic ★ same condition
AARS1 p.Ala656fs Pathogenic ★ same condition
AARS1 p.Lys846_Gln847delinsAsnTer Pathogenic ★ same condition
AARS1 c.2521-4_2521-3delinsAA Uncertain significance ★ same condition
AARS1 p.His727Tyr Uncertain significance ★ same condition
AARS1 p.Ser851Lys 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/aars1-p-gln381ter (accessed [today's date]).

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