Is MARS1 p.Pro206= (c.618C>T) pathogenic?

MARS1 p.Pro206= (c.618C>T) is classified Likely benign in MARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). Absent from gnomAD v4.1; Associated with severe early-onset pulmonary alveolar proteinosis due to MARS deficiency.

How common is MARS1 p.Pro206= (c.618C>T) in the general population?

MARS1 p.Pro206= (c.618C>T) is absent from gnomAD v4.1 (gnomAD).

MARS1 p.Pro206=

Q: What condition is associated with MARS1 p.Pro206= (c.618C>T)?

MARS1 p.Pro206= (c.618C>T) is associated with severe early-onset pulmonary alveolar proteinosis due to MARS deficiency, Charcot-Marie-Tooth disease axonal type 2U (ClinVar).

Q: How is Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency inherited?

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

c.618C>T · rs2540261194 · VCV2943023

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

severe early-onset pulmonary alveolar proteinosis due to MARS deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.076	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -0.055
Overall
CADD	7.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MARS1
Protein: p.Pro206=
Coding: c.618C>T
MANE Select: NM_004990
dbSNP: rs2540261194
Type: single nucleotide variant
Location: chr12:57490334 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.61 · 7 PDB
Residue 206: a UniProt-annotated variant site (in)

Full MARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe early-onset pulmonary alveolar proteinosis due to MARS deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2U

For Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MARS1 p.Pro206Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MARS1 p.Pro206Ser Uncertain significance ★ ⚠ same residue
MARS1 c.1293+5G>A Uncertain significance ★★ same condition
MARS1 c.1967+3A>G Uncertain significance ★★ same condition
MARS1 p.Ala160Thr Uncertain significance ★★ ⚠ same condition
MARS1 p.Ala211Thr Uncertain significance ★★ ⚠ same condition
MARS1 p.Ala261Val Uncertain significance ★★ ⚠ same condition
MARS1 p.Ala397Thr 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/mars1-p-pro206 (accessed [today's date]).

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