Is AARS2 p.Arg722Trp (c.2164C>T) pathogenic?

AARS2 p.Arg722Trp (c.2164C>T) is classified Likely benign in AARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.1892); Rare (popmax 0.163%, afr).

How common is AARS2 p.Arg722Trp (c.2164C>T) in the general population?

AARS2 p.Arg722Trp (c.2164C>T) is rare (popmax 0.163%, afr) (gnomAD).

What do computational predictors say about AARS2 p.Arg722Trp (c.2164C>T)?

AlphaMissense predicts likely benign (score 0.1892) — an in-silico prediction, not a clinical call.

AARS2 p.Arg722Trp

c.2164C>T · rs145436818 · VCV1430809

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1892 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1892	likely benign
REVEL	0.717	pathogenic-leaning
SaProt	LLR -13.07	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Pangolin	Δ0.31	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.00019 · regional, not allelic
Overall
CADD	32.0	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 0.163% African / African-American · 122/75,048 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.0121% 196/1,614,138 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	615
Admixed American	0.0617%	1,622
East Asian	0.0356%	2,805
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Middle Eastern	0.0165%	6,062
South Asian	0.00439%	22,770
Finnishnot grpmax-eligible	0.00156%	63,992
European (non-Finnish)	0.000339%	295,006

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.Arg722Trp
Coding: c.2164C>T
MANE Select: NM_020745
dbSNP: rs145436818
Type: single nucleotide variant
Location: chr6:44303157 (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.Arg722Gln Uncertain significance ★★ ⚠ 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
AARS2 p.Arg592Trp Pathogenic/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-arg722trp (accessed [today's date]).

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