Is MARS1 p.Pro10= (c.30G>A) pathogenic?

MARS1 p.Pro10= (c.30G>A) is classified Likely benign in MARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-19). Very rare (popmax 0.00492%, nfe); Associated with severe early-onset pulmonary alveolar proteinosis due to MARS deficiency.

How common is MARS1 p.Pro10= (c.30G>A) in the general population?

MARS1 p.Pro10= (c.30G>A) is very rare (popmax 0.00492%, nfe) (gnomAD).

MARS1 p.Pro10=

Q: What condition is associated with MARS1 p.Pro10= (c.30G>A)?

MARS1 p.Pro10= (c.30G>A) 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.30G>A · rs751620229 · VCV2923691

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

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 0.2	GERP -3.2, phastCons 0.92
Overall
CADD	9.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 58/1,180,034 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00613% 99/1,614,038 alleles · very rare exomes 84/1,461,846 · genomes 15/152,192 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0578%	1,730
European (non-Finnish)grpmax	0.00492%	20,345
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,462

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro10=
Coding: c.30G>A
MANE Select: NM_004990
dbSNP: rs751620229
Type: single nucleotide variant
Location: chr12:57488120 (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-pro10 (accessed [today's date]).

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