Is RARS2 p.Arg86= (c.258G>A) pathogenic?

RARS2 p.Arg86= (c.258G>A) is classified Uncertain significance in RARS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-12). Absent from gnomAD v4.1; Associated with pontocerebellar hypoplasia type 6.

What condition is associated with RARS2 p.Arg86= (c.258G>A)?

RARS2 p.Arg86= (c.258G>A) is associated with pontocerebellar hypoplasia type 6 (ClinVar).

How common is RARS2 p.Arg86= (c.258G>A) in the general population?

RARS2 p.Arg86= (c.258G>A) is absent from gnomAD v4.1 (gnomAD).

RARS2 p.Arg86=

c.258G>A · VCV4060734

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pontocerebellar hypoplasia type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -2.5
Overall
CADD	7.492	PHRED · no single calibrated threshold — expert panels disagree

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: RARS2
Protein: p.Arg86=
Coding: c.258G>A
MANE Select: NM_020320
Type: single nucleotide variant
Location: chr6:87562741 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.18

Full RARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RARS2 c.1035+2T>G Likely pathogenic ★★ same condition
RARS2 c.110+5A>G Pathogenic/Likely pathogenic ★★ same condition
RARS2 c.111-2A>G Likely pathogenic ★★ same condition
RARS2 c.1113-2A>G Likely pathogenic ★★ same condition
RARS2 c.1237+1G>A Pathogenic/Likely pathogenic ★★ same condition
RARS2 c.1237+1G>C Likely pathogenic ★★ same condition
RARS2 c.1238-2A>G Likely pathogenic ★★ same condition
RARS2 c.1415+1G>A Likely pathogenic ★★ 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/rars2-p-arg86 (accessed [today's date]).

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