Is AARS2 p.Arg10Gln (c.29G>A) pathogenic?

AARS2 p.Arg10Gln (c.29G>A) is classified Likely benign in AARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.1713); Ultra-rare (popmax 0.0591%, mid).

How common is AARS2 p.Arg10Gln (c.29G>A) in the general population?

AARS2 p.Arg10Gln (c.29G>A) is ultra-rare (popmax 0.0591%, mid) (gnomAD).

What do computational predictors say about AARS2 p.Arg10Gln (c.29G>A)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

AARS2 p.Arg10Gln

c.29G>A · VCV4751248

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0591%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -3
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.00019 · regional, not allelic
Overall
CADD	8.077	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0591% Middle Eastern · 3/5,078 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00231% 37/1,598,330 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0591%	1,693
African / African-American	0.0361%	2,768
Admixed American	0.00679%	14,731
Remaining individualsnot grpmax-eligible	0.00323%	30,958
European (non-Finnish)	8.5e-05%	1,176,950

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.Arg10Gln
Coding: c.29G>A
MANE Select: NM_020745
Type: single nucleotide variant
Location: chr6:44313295 (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.Arg10Gly Uncertain significance ★ ⚠ same residue
AARS2 p.Arg10= Likely benign ★ 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
AARS2 p.Arg580Trp Likely 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-arg10gln (accessed [today's date]).

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