Is AARS2 p.His632Arg (c.1895A>G) pathogenic?

AARS2 p.His632Arg (c.1895A>G) is classified Uncertain significance in AARS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-02-25). AlphaMissense: likely pathogenic (0.8124); Absent from gnomAD v4.1.

How common is AARS2 p.His632Arg (c.1895A>G) in the general population?

AARS2 p.His632Arg (c.1895A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AARS2 p.His632Arg (c.1895A>G)?

AlphaMissense predicts likely pathogenic (score 0.8124) — an in-silico prediction, not a clinical call.

AARS2 p.His632Arg

c.1895A>G · rs1554148040 · VCV559278

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8124 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8124	likely pathogenic · top 9% in AARS2
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.00019 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AARS2
Protein: p.His632Arg
Coding: c.1895A>G
MANE Select: NM_020745
dbSNP: rs1554148040
Type: single nucleotide variant
Location: chr6:44304293 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.05 · 3 PDB
Residue 632: a binding site

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

Similar variants

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
AARS2 p.Arg958Ter 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-his632arg (accessed [today's date]).

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