Is GARS1 p.Asp205= (c.615C>T) pathogenic?

GARS1 p.Asp205= (c.615C>T) is classified Likely benign in GARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with GARS1 p.Asp205= (c.615C>T)?

GARS1 p.Asp205= (c.615C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is GARS1 p.Asp205= (c.615C>T) in the general population?

GARS1 p.Asp205= (c.615C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

GARS1 p.Asp205=

c.615C>T · rs370008019 · VCV1145991

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -4	GERP -3.8
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00136% 22/1,613,784 alleles · ultra-rare exomes 19/1,461,550 · genomes 3/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Finnishnot grpmax-eligible	0.00312%	32,005
East Asian	0.00223%	44,792
European (non-Finnish)	0.00144%	69,403
South Asian	0.0011%	91,082

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.Asp205=
Coding: c.615C>T
MANE Select: NM_002047
dbSNP: rs370008019
Type: single nucleotide variant
Location: chr7:30603079 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 14 PDB
Residue 205: a β-strand

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.Asp205Val Uncertain significance ★★ ⚠ same residue
GARS1 p.Asp205His 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

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-asp205 (accessed [today's date]).

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