Is GARS1 p.Ser54= (c.162C>T) pathogenic?

GARS1 p.Ser54= (c.162C>T) is classified Likely benign in GARS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-18). Very rare (popmax 0.00217%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with GARS1 p.Ser54= (c.162C>T)?

GARS1 p.Ser54= (c.162C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Ser54= (c.162C>T) in the general population?

GARS1 p.Ser54= (c.162C>T) is very rare (popmax 0.00217%, nfe) (gnomAD).

GARS1 p.Ser54=

c.162C>T · rs758434035 · VCV574424

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00217%, nfe)

Conditions

Charcot-Marie-Tooth disease type 2

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 5.6	GERP 0.41, phastCons 1
Overall
CADD	16.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% European (non-Finnish) · 25/1,151,746 alleles

Filtering AF 0.00149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.00186% 26/1,394,368 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00217%	46,070
Remaining individualsnot grpmax-eligible	0.00166%	60,390

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.Ser54=
Coding: c.162C>T
MANE Select: NM_002047
dbSNP: rs758434035
Type: single nucleotide variant
Location: chr7:30595083 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB

Full GARS1 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

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-ser54 (accessed [today's date]).

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