Is AARS1 p.Arg511= (c.1533G>A) pathogenic?

AARS1 p.Arg511= (c.1533G>A) is classified Likely benign in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-28). Very rare (popmax 0.00712%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Arg511= (c.1533G>A)?

AARS1 p.Arg511= (c.1533G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Arg511= (c.1533G>A) in the general population?

AARS1 p.Arg511= (c.1533G>A) is very rare (popmax 0.00712%, nfe) (gnomAD).

AARS1 p.Arg511=

c.1533G>A · rs375230340 · VCV1682214

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00712%, nfe)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP 0.86, phastCons 1
Overall
CADD	14.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00712% European (non-Finnish) · 84/1,180,024 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00527% 85/1,614,024 alleles · very rare exomes 83/1,461,844 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00712%	14,048
African / African-American	0.00133%	74,926

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: AARS1
Protein: p.Arg511=
Coding: c.1533G>A
MANE Select: NM_001605
dbSNP: rs375230340
Type: single nucleotide variant
Location: chr16:70262484 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB

Full AARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg13Ter Pathogenic ★★ same condition
AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg329Cys Likely pathogenic ★★ same condition
AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg333Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg598Ter Pathogenic/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/aars1-p-arg511 (accessed [today's date]).

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