Is GARS1 p.Phe579= (c.1737C>T) pathogenic?

GARS1 p.Phe579= (c.1737C>T) is classified Likely benign in GARS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-17). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease.

What condition is associated with GARS1 p.Phe579= (c.1737C>T)?

GARS1 p.Phe579= (c.1737C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Phe579= (c.1737C>T) in the general population?

GARS1 p.Phe579= (c.1737C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

GARS1 p.Phe579=

c.1737C>T · rs752464405 · VCV258534

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.9	GERP -2.7, phastCons 0.011
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00136% 22/1,612,840 alleles · ultra-rare exomes 17/1,460,646 · genomes 5/152,194 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,406
Finnishnot grpmax-eligible	0.00156%	63,990
European (non-Finnish)	0.00136%	73,694
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,068

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.Phe579=
Coding: c.1737C>T
MANE Select: NM_002047
dbSNP: rs752464405
Type: single nucleotide variant
Location: chr7:30628597 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB
Residue 579: a β-strand

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 2

Similar variants

GARS1 p.Phe579fs Uncertain significance ★ same residue
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

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-phe579 (accessed [today's date]).

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