Is NARS2 p.Glu450= (c.1350A>G) pathogenic?

NARS2 p.Glu450= (c.1350A>G) is classified Likely benign in NARS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-08). Very rare (popmax 0.00549%, sas); Associated with NARS2-related disorder.

What condition is associated with NARS2 p.Glu450= (c.1350A>G)?

NARS2 p.Glu450= (c.1350A>G) is associated with NARS2-related disorder (ClinVar).

How common is NARS2 p.Glu450= (c.1350A>G) in the general population?

NARS2 p.Glu450= (c.1350A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

NARS2 p.Glu450=

c.1350A>G · rs1281406867 · VCV3058399

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

NARS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.292	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.24, phastCons 1
Overall
CADD	9.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,092 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000372% 6/1,614,208 alleles · very rare exomes 6/1,461,868 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: NARS2
Protein: p.Glu450=
Coding: c.1350A>G
MANE Select: NM_024678
dbSNP: rs1281406867
Type: single nucleotide variant
Location: chr11:78436754 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.59
Residue 450: a UniProt-annotated variant site (in coxpd24)

Full NARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NARS2-related disorder

Similar variants

NARS2 p.Glu193Ter Likely pathogenic ★ same condition
NARS2 p.Gly344Arg Uncertain significance ★ ⚠ same condition
NARS2 p.Ile462Thr Uncertain significance ★ ⚠ same condition
NARS2 p.Thr149= Likely benign same condition
NARS2 p.Val235= Likely benign same condition
NARS2 p.Glu42fs Likely pathogenic ★★ same condition
NARS2 c.1165-8_1165-7del Likely benign same condition
NARS2 p.Arg140Ter 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/nars2-p-glu450 (accessed [today's date]).

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