MRAS p.Ala145=
c.435G>A · rs754375420 · VCV1646769
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -2.9 | GERP -3.9 |
| Overall | ||
| CADD | 7.131 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,072 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000434%
7/1,613,980 alleles · very rare
exomes 6/1,461,830 · genomes 1/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,536 |
| African / African-American | 0.00133% | 74,912 |
| European (non-Finnish) | 0.000339% | 295,001 |
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.Ala145=
- Coding
- c.435G>A
- MANE Select
- NM_001085049
- dbSNP
- rs754375420
- Type
- single nucleotide variant
- Location
- chr3:138398556 (GRCh38)
- Gene constraint
- LOEUF 0.444 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 11 PDB
- Residue 145
- an α-helix
Similar variants
- MRAS p.Ala145Glu Uncertain significance ★ ⚠ same residue
- MRAS p.Ala145Val Uncertain significance ★ ⚠ same residue
- MRAS p.Gln71Arg Likely pathogenic ★★★ same type
- MRAS p.Gly23Arg Likely pathogenic ★★★ same type
- MRAS p.Gly23Val Likely pathogenic ★★★ same type
- MRAS p.Thr68Ile Likely pathogenic ★★★ same type
- MRAS p.Gln59= Benign ★★★ same type
- MRAS p.Pro151= Benign ★★★ 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-ala145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown