Is AARS2 p.Thr910= (c.2730G>A) pathogenic?

AARS2 p.Thr910= (c.2730G>A) is classified Likely benign in AARS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-13). Ultra-rare (popmax 0.0624%, eas).

How common is AARS2 p.Thr910= (c.2730G>A) in the general population?

AARS2 p.Thr910= (c.2730G>A) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

AARS2 p.Thr910=

c.2730G>A · rs201616927 · VCV384888

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

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 -4.4
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0624% East Asian · 28/44,872 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00552% 89/1,613,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,603
Admixed American	0.00667%	14,991
Remaining individualsnot grpmax-eligible	0.0064%	15,620
African / African-American	0.00533%	18,755
European (non-Finnish)	0.00407%	24,583
South Asian	0.0011%	91,080

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: AARS2
Protein: p.Thr910=
Coding: c.2730G>A
MANE Select: NM_020745
dbSNP: rs201616927
Type: single nucleotide variant
Location: chr6:44301219 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.05 · 3 PDB

Full AARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AARS2 p.Thr910Arg Uncertain significance ★ ⚠ same residue
AARS2 p.Thr910Met Uncertain significance ★ ⚠ same residue
AARS2 p.Thr910fs Conflicting classifications of pathogenicity ★ same residue
AARS2 c.2146-2A>G Pathogenic/Likely pathogenic ★★ same type
AARS2 c.2255+1G>A Pathogenic ★★ same type
AARS2 c.2598+1G>T Pathogenic/Likely pathogenic ★★ same type
AARS2 p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
AARS2 p.Arg521Ter Pathogenic ★★ same type

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/aars2-p-thr910 (accessed [today's date]).

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