Is NARS2 p.Arg84= (c.252A>G) pathogenic?

NARS2 p.Arg84= (c.252A>G) is classified Likely benign in NARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). Rare (popmax 0.217%, mid); Associated with Inborn genetic diseases.

What condition is associated with NARS2 p.Arg84= (c.252A>G)?

NARS2 p.Arg84= (c.252A>G) is associated with Inborn genetic diseases (ClinVar).

How common is NARS2 p.Arg84= (c.252A>G) in the general population?

NARS2 p.Arg84= (c.252A>G) is rare (popmax 0.217%, mid) (gnomAD).

NARS2 p.Arg84=

c.252A>G · VCV4116866

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.217%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.93, phastCons 1
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.217% Middle Eastern · 13/5,992 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00107% 17/1,593,856 alleles · rare exomes 17/1,441,566 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.217%	461
Remaining individualsnot grpmax-eligible	0.00486%	20,566
South Asian	0.00113%	88,312

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.Arg84=
Coding: c.252A>G
MANE Select: NM_024678
Type: single nucleotide variant
Location: chr11:78568752 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.59

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NARS2 p.Ala17Val Uncertain significance ★★ ⚠ same condition
NARS2 p.Arg243Gln Uncertain significance ★★ ⚠ same condition
NARS2 p.Arg436Gln Uncertain significance ★★ ⚠ same condition
NARS2 p.Arg43Cys Uncertain significance ★★ ⚠ same condition
NARS2 p.Asn461Ser Uncertain significance ★★ ⚠ same condition
NARS2 p.Glu416Gln Uncertain significance ★★ ⚠ same condition
NARS2 p.His413Asp Uncertain significance ★★ ⚠ same condition
NARS2 p.Ile115Val Uncertain significance ★★ ⚠ same condition

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-arg84 (accessed [today's date]).

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