Is GARS1 p.Asp90= (c.270C>T) pathogenic?

GARS1 p.Asp90= (c.270C>T) is classified Benign/Likely benign in GARS1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-17). Rare (popmax 0.264%, mid); Associated with distal hereditary motor neuropathy.

What condition is associated with GARS1 p.Asp90= (c.270C>T)?

GARS1 p.Asp90= (c.270C>T) is associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease type 2D, neuronopathy, distal hereditary motor, type 5A (ClinVar).

How common is GARS1 p.Asp90= (c.270C>T) in the general population?

GARS1 p.Asp90= (c.270C>T) is rare (popmax 0.264%, mid) (gnomAD).

GARS1 p.Asp90=

c.270C>T · rs369898799 · VCV360002

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.264%, mid)

Conditions

distal hereditary motor neuropathy

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 0.61	GERP -2.8, phastCons 1
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% Middle Eastern · 16/6,060 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.018% 291/1,614,112 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.264%	379
South Asian	0.108%	929
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.0167%	6,002
European (non-Finnish)	0.0119%	8,429
East Asian	0.00223%	44,888
African / African-American	0.00133%	75,010

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: GARS1
Protein: p.Asp90=
Coding: c.270C>T
MANE Select: NM_002047
dbSNP: rs369898799
Type: single nucleotide variant
Location: chr7:30598843 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB
Residue 90: the whep-trs domain

Full GARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

distal hereditary motor neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2D neuronopathy, distal hereditary motor, type 5A Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease type 2

Similar variants

GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.His472Arg Pathogenic ★★ same condition
GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Ile334Phe Pathogenic ★★ same condition
GARS1 p.Ile334Thr Pathogenic/Likely pathogenic ★★ same condition
GARS1 p.Ser265Phe 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/gars1-p-asp90 (accessed [today's date]).

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