Is MARS2 p.Trp151Ser (c.452G>C) pathogenic?

MARS2 p.Trp151Ser (c.452G>C) is classified Uncertain significance in MARS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.8971); Very rare (popmax 0.0061%, nfe).

How common is MARS2 p.Trp151Ser (c.452G>C) in the general population?

MARS2 p.Trp151Ser (c.452G>C) is very rare (popmax 0.0061%, nfe) (gnomAD).

What do computational predictors say about MARS2 p.Trp151Ser (c.452G>C)?

AlphaMissense predicts likely pathogenic (score 0.8971) — an in-silico prediction, not a clinical call.

MARS2 p.Trp151Ser

c.452G>C · rs746799979 · VCV2906035

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0061%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8971	likely pathogenic
REVEL	0.715	pathogenic-leaning
SaProt	LLR -16.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,778 bp · p 0.12 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% European (non-Finnish) · 72/1,180,034 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00465% 75/1,613,700 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0061%	16,389
South Asian	0.00329%	30,363

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.Trp151Ser
Coding: c.452G>C
MANE Select: NM_138395
dbSNP: rs746799979
Type: single nucleotide variant
Location: chr2:197705857 (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.Trp151Leu Uncertain significance ★★ ⚠ same residue
MARS2 p.Trp151Cys Uncertain significance ★ ⚠ same residue
MARS2 p.Trp151Ter Uncertain significance ★ same residue
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

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-trp151ser (accessed [today's date]).

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