MRAS p.Pro151=
c.453G>A · rs149904534 · VCV496410
ClinGen expert panel — RASopathy VCEP
Benign for RASopathy. Applied ACMG criteria (verbatim):
BA1
Curation rationale (ClinGen, verbatim)
The c.453G>A (p.Pro151=) variant in MRAS is a synonymous variant at position 151. This variant has a filtering allele frequency of 1.748% in the South Asian population in gnomAD v2, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1 (RASopathy VCEP specifications version 1.4; 12/3/2024)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.2 |
| Overall | ||
| CADD | 1.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.88% | 53 |
| Middle Eastern | 1.47% | 68 |
| Ashkenazi Jewishnot grpmax-eligible | 1.16% | 87 |
| Remaining individualsnot grpmax-eligible | 0.304% | 329 |
| Admixed American | 0.152% | 659 |
| European (non-Finnish) | 0.0752% | 1,330 |
| African / African-American | 0.0213% | 4,687 |
| East Asian | 0.00446% | 22,430 |
| Finnishnot grpmax-eligible | 0.00156% | 64,016 |
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
- MRAS
- Protein
- p.Pro151=
- Coding
- c.453G>A
- MANE Select
- NM_001085049
- dbSNP
- rs149904534
- Type
- single nucleotide variant
- Location
- chr3:138400539 (GRCh38)
- Gene constraint
- LOEUF 0.444 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 11 PDB
Similar variants
- MRAS p.Pro151Leu Uncertain significance ★ ⚠ same residue
- MRAS p.Gln71Arg Likely pathogenic ★★★ same condition
- MRAS p.Gly23Arg Likely pathogenic ★★★ same condition
- MRAS p.Gly23Val Likely pathogenic ★★★ same condition
- MRAS p.Thr68Ile Likely pathogenic ★★★ same condition
- MRAS p.Gln59= Benign ★★★ same condition
- MRAS c.528-2del Benign ★★★ same condition
- MRAS p.Ala167Gly 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/mras-p-pro151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown