Is MARS2 p.Arg12= (c.36C>T) pathogenic?

MARS2 p.Arg12= (c.36C>T) is classified Likely benign in MARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Rare (popmax 0.112%, sas).

How common is MARS2 p.Arg12= (c.36C>T) in the general population?

MARS2 p.Arg12= (c.36C>T) is rare (popmax 0.112%, sas) (gnomAD).

MARS2 p.Arg12=

c.36C>T · VCV3898474

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.112%, sas)

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 0.43	GERP -0.97, phastCons 0.005
Overall
CADD	7.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% South Asian · 102/91,040 alleles

Filtering AF 0.0944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.00676% 109/1,612,238 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.112%	893
Remaining individualsnot grpmax-eligible	0.00961%	10,407
European (non-Finnish)	8.48e-05%	1,179,800

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: MARS2
Protein: p.Arg12=
Coding: c.36C>T
MANE Select: NM_138395
Type: single nucleotide variant
Location: chr2:197705441 (GRCh38)
Gene constraint: LOEUF 0.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66

Full MARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARS2 p.Ala141Val Uncertain significance ★★ ⚠ same type
MARS2 p.Ala402Ser Uncertain significance ★★ ⚠ same type
MARS2 p.Arg142Trp Uncertain significance ★★ ⚠ same type
MARS2 p.Arg224Gln Uncertain significance ★★ ⚠ same type
MARS2 p.Arg409Gly Uncertain significance ★★ ⚠ same type
MARS2 p.Arg414Ile Uncertain significance ★★ ⚠ same type
MARS2 p.Arg568Gly Uncertain significance ★★ ⚠ same type
MARS2 p.Arg592Gln Uncertain significance ★★ ⚠ same type

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/mars2-p-arg12 (accessed [today's date]).

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