NRAS p.Leu120=
c.360G>A · rs143020946 · VCV40476
ClinGen expert panel — RASopathy VCEP
Likely Benign for RASopathy. Applied ACMG criteria (verbatim):
BS1 BP5 BP7 BP4
Curation rationale (ClinGen, verbatim)
The NM_002524.5:c.360G>A (p.Leu120=) variant is a synonymous (silent) variant in NRAS that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 77/129188) of the c.360G>A variant in NRAS is 0.0004832 for European (non-Finnish) chromosomes by gnomAD v2.1.1, which is higher than the ClinGen RASopathy VCEP threshold (≥0.00025) for BS1, and therefore meets this criterion (BS1). Observed in 1 individual with a co-occurring likely pathogenic/pathogenic variant in a gene that explains their condition, Noonan syndrome (Invitae internal data, ClinVar SCV000253394.6). In summary, this variant meets the criteria to be classified as likely benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BS1, BP4, BP5, BP7. (ClinGen RASopathy VCEP specifications version 2.3; 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -0.22, phastCons 1 |
| Overall | ||
| CADD | 10.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0683% | 1,463 |
| Remaining individualsnot grpmax-eligible | 0.0512% | 1,952 |
| Middle Eastern | 0.0495% | 2,019 |
| Admixed American | 0.0217% | 4,616 |
| African / African-American | 0.00933% | 10,713 |
| Finnishnot grpmax-eligible | 0.00312% | 32,018 |
| South Asian | 0.0011% | 91,064 |
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
- NRAS
- Protein
- p.Leu120=
- Coding
- c.360G>A
- MANE Select
- NM_002524
- dbSNP
- rs143020946
- Type
- single nucleotide variant
- Location
- chr1:114709659 (GRCh38)
- Gene constraint
- LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.56 · 36 PDB
Similar variants
- NRAS p.Gly12Ser Pathogenic ★★★ same condition
- NRAS p.Gly60Glu Pathogenic ★★★ same condition
- NRAS p.Ile24Asn Likely pathogenic ★★★ same condition
- NRAS p.Thr50Ile Pathogenic ★★★ ⚠ same condition
- NRAS p.Thr58Ile Pathogenic ★★★ same condition
- NRAS p.Ala11Thr Uncertain significance ★★★ ⚠ same condition
- NRAS p.Ala91Val Uncertain significance ★★★ ⚠ same condition
- NRAS p.Arg123Lys Uncertain significance ★★★ ⚠ same condition
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/nras-p-leu120 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown