Is YARS1 p.Pro360= (c.1080A>G) pathogenic?

YARS1 p.Pro360= (c.1080A>G) is classified Benign/Likely benign in YARS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00329%, sas); Associated with Charcot-Marie-Tooth disease dominant intermediate C.

What condition is associated with YARS1 p.Pro360= (c.1080A>G)?

YARS1 p.Pro360= (c.1080A>G) is associated with Charcot-Marie-Tooth disease dominant intermediate C (ClinVar).

How common is YARS1 p.Pro360= (c.1080A>G) in the general population?

YARS1 p.Pro360= (c.1080A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

YARS1 p.Pro360=

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type C inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1080A>G · rs752514117 · VCV697544

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Charcot-Marie-Tooth disease dominant intermediate C

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 0.057	GERP -0.71, phastCons 0.97
Overall
CADD	10.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,094 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00211% 34/1,614,124 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,365
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.00246%	40,692

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: YARS1
Protein: p.Pro360=
Coding: c.1080A>G
MANE Select: NM_003680
dbSNP: rs752514117
Type: single nucleotide variant
Location: chr1:32781108 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.12 · 8 PDB
Residue 360: the 'disordered' region

Full YARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type C (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

YARS1 p.Pro360Ala Uncertain significance ★★ ⚠ same residue
YARS1 p.Pro360Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
YARS1 p.Glu196Gln Pathogenic/Likely pathogenic ★★ same condition
YARS1 p.Glu196Lys Pathogenic/Likely pathogenic ★★ same condition
YARS1 p.Pro167Thr Pathogenic/Likely pathogenic ★★ same condition
YARS1 c.1042+3A>C Uncertain significance ★★ same condition
YARS1 c.58-2A>G Uncertain significance ★★ same condition
YARS1 c.*539A>G Uncertain significance ★★ 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/yars1-p-pro360 (accessed [today's date]).

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