Is AARS1 p.Thr900= (c.2700G>A) pathogenic?

AARS1 p.Thr900= (c.2700G>A) is classified Benign/Likely benign in AARS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0691%, eas); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Thr900= (c.2700G>A)?

AARS1 p.Thr900= (c.2700G>A) 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.Thr900= (c.2700G>A) in the general population?

AARS1 p.Thr900= (c.2700G>A) is ultra-rare (popmax 0.0691%, eas) (gnomAD).

AARS1 p.Thr900=

c.2700G>A · rs140814462 · VCV320326

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0691%, 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 -20	GERP -2.8
Overall
CADD	0.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0691% East Asian · 31/44,878 alleles

Filtering AF 0.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.0159% 257/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0691%	1,448
European (non-Finnish)	0.0177%	5,645
Admixed American	0.0167%	6,003
Remaining individualsnot grpmax-eligible	0.0096%	10,417
African / African-American	0.00133%	75,052

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.Thr900=
Coding: c.2700G>A
MANE Select: NM_001605
dbSNP: rs140814462
Type: single nucleotide variant
Location: chr16:70253289 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 900: a β-strand

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.Thr900Met 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
AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg333Ter Pathogenic/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-thr900 (accessed [today's date]).

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