Is MARS1 p.Pro14= (c.42G>T) pathogenic?

MARS1 p.Pro14= (c.42G>T) is classified Likely benign in MARS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-22). Rare (popmax 0.111%, afr); Associated with severe early-onset pulmonary alveolar proteinosis due to MARS deficiency.

How common is MARS1 p.Pro14= (c.42G>T) in the general population?

MARS1 p.Pro14= (c.42G>T) is rare (popmax 0.111%, afr) (gnomAD).

MARS1 p.Pro14=

Q: What condition is associated with MARS1 p.Pro14= (c.42G>T)?

MARS1 p.Pro14= (c.42G>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.42G>T · rs144002827 · VCV386932

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.111%, afr)

Conditions

severe early-onset pulmonary alveolar proteinosis due to MARS deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -11	GERP -3.2
Overall
CADD	0.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% African / African-American · 83/75,056 alleles

Filtering AF 0.0914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0843%

Overall 0.00719% 116/1,614,174 alleles · rare exomes 66/1,461,850 · genomes 50/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	904
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.015%	6,669
European (non-Finnish)	0.00102%	98,337

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: MARS1
Protein: p.Pro14=
Coding: c.42G>T
MANE Select: NM_004990
dbSNP: rs144002827
Type: single nucleotide variant
Location: chr12:57488132 (GRCh38)

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

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-pro14 (accessed [today's date]).

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