Is AARS1 p.Ile579= (c.1737C>T) pathogenic?

AARS1 p.Ile579= (c.1737C>T) is classified Benign/Likely benign in AARS1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). Rare (popmax 0.512%, mid); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Ile579= (c.1737C>T)?

AARS1 p.Ile579= (c.1737C>T) is associated with Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease axonal type 2N (ClinVar).

How common is AARS1 p.Ile579= (c.1737C>T) in the general population?

AARS1 p.Ile579= (c.1737C>T) is rare (popmax 0.512%, mid) (gnomAD).

AARS1 p.Ile579=

c.1737C>T · rs144323646 · VCV320337

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.512%, mid)

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 0.68	GERP -0.18, phastCons 1
Overall
CADD	3.488	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.512% Middle Eastern · 31/6,060 alleles

Filtering AF 0.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.322%

Overall 0.113% 1,824/1,613,918 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.512%	195
Ashkenazi Jewishnot grpmax-eligible	0.263%	380
Admixed American	0.148%	674
Remaining individualsnot grpmax-eligible	0.144%	694
European (non-Finnish)	0.124%	804
South Asian	0.0483%	2,070
African / African-American	0.032%	3,125
Finnishnot grpmax-eligible	0.00156%	64,018

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: AARS1
Protein: p.Ile579=
Coding: c.1737C>T
MANE Select: NM_001605
dbSNP: rs144323646
Type: single nucleotide variant
Location: chr16:70261092 (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

Also linked: Charcot-Marie-Tooth disease axonal type 2N

Similar variants

AARS1 p.Ile579Met Conflicting classifications of pathogenicity ★ ⚠ same residue
AARS1 p.Ile579Phe Uncertain significance ★ ⚠ same residue
AARS1 p.Ile579Thr Uncertain significance ★ ⚠ same residue
AARS1 p.Ile579Val Uncertain significance ★ ⚠ same residue
AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg13Ter Pathogenic ★★ same condition
AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg329Cys 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/aars1-p-ile579 (accessed [today's date]).

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