Is AARS1 p.Gln541fs (c.1618_1619dup) pathogenic?

AARS1 p.Gln541fs (c.16181619dup) is classified Pathogenic in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Gln541fs (c.1618_1619dup)?

AARS1 p.Gln541fs (c.1618_1619dup) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Gln541fs (c.1618_1619dup) in the general population?

AARS1 p.Gln541fs (c.1618_1619dup) is absent from gnomAD (gnomAD).

AARS1 p.Gln541fs

c.1618_1619dup · rs1567604571 · VCV577403

Pathogenic Single submitter

Classification

Pathogenic

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 12 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -3.7, phastCons 0.001

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.Gln541fs
Coding: c.1618_1619dup
MANE Select: NM_001605
dbSNP: rs1567604571
Type: Duplication
Location: chr16:70262397 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB

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.Gln541Arg Uncertain significance ★ ⚠ same residue
AARS1 c.2722-28_2740dup Uncertain significance ★★ same condition
AARS1 p.Leu877fs Pathogenic ★ same condition
AARS1 p.Ser249fs Pathogenic ★ same condition
AARS1 p.Thr38fs Pathogenic ★ same condition
AARS1 p.Tyr497Ter Pathogenic ★ same condition
AARS1 p.Pro693_Val694insAspPro Uncertain significance ★ same condition
AARS1 c.144+12dup Benign ★ 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-gln541fs (accessed [today's date]).

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