Is AARS2 p.Asp337Ter (c.1008dup) pathogenic?

AARS2 p.Asp337Ter (c.1008dup) is classified Pathogenic in AARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-18). Very rare (popmax 0.00466%, nfe).

How common is AARS2 p.Asp337Ter (c.1008dup) in the general population?

AARS2 p.Asp337Ter (c.1008dup) is very rare (popmax 0.00466%, nfe) (gnomAD).

AARS2 p.Asp337Ter

c.1008dup · rs766771165 · VCV213970

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00466% European (non-Finnish) · 55/1,179,946 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.0039% 57/1,461,700 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00466%	21,454
Remaining individualsnot grpmax-eligible	0.0032%	31,250

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.Asp337Ter
Coding: c.1008dup
MANE Select: NM_020745
dbSNP: rs766771165
Type: Duplication
Location: chr6:44307280 (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.Cys218fs Pathogenic ★★ same type
AARS2 p.Ala39fs Likely pathogenic ★ same type
AARS2 p.Gln236fs Likely pathogenic ★ same type
AARS2 p.Ile884fs Likely pathogenic ★ same type
AARS2 p.Leu30fs Pathogenic ★ same type
AARS2 p.Met920fs Pathogenic ★ same type
AARS2 p.Ala407_Phe408insAspGluAlaAla Uncertain significance ★ same type
AARS2 p.Lys953fs Uncertain significance ★ 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-asp337ter (accessed [today's date]).

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