Is AARS1 p.Ile470= (c.1410C>T) pathogenic?

AARS1 p.Ile470= (c.1410C>T) is classified Benign/Likely benign in AARS1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.225%, eas); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Ile470= (c.1410C>T)?

AARS1 p.Ile470= (c.1410C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2N, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Ile470= (c.1410C>T) in the general population?

AARS1 p.Ile470= (c.1410C>T) is rare (popmax 0.225%, eas) (gnomAD).

AARS1 p.Ile470=

c.1410C>T · rs79785372 · VCV320342

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.225%, eas)

Conditions

Inborn genetic diseases

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 -1.8	GERP -3.7
Overall
CADD	4.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.225% East Asian · 101/44,878 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.0142% 229/1,614,120 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.225%	444
South Asian	0.0966%	1,035
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Middle Eastern	0.0165%	6,060
Admixed American	0.00333%	30,000
African / African-American	0.00267%	37,512
European (non-Finnish)	0.000678%	147,503

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.Ile470=
Coding: c.1410C>T
MANE Select: NM_001605
dbSNP: rs79785372
Type: single nucleotide variant
Location: chr16:70265040 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

AARS1 p.Ile470Asn Uncertain significance ★★ ⚠ same residue
AARS1 p.Ile470Phe Uncertain significance ★★ ⚠ same residue
AARS1 p.Ile470Met Uncertain significance ★ ⚠ same residue
AARS1 p.Ile470Val 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-ile470 (accessed [today's date]).

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