HRAS p.Asp119=
c.357C>T · rs111352454 · VCV40441
ClinGen expert panel — RASopathy VCEP
Benign for RASopathy. Applied ACMG criteria (verbatim):
BA1
Curation rationale (ClinGen, verbatim)
The filtering allele frequency of the c.357C>T (p.Asp119=) variant in the HRAS gene is 0.129% (102/66416) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
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 2.4 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 6.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.285% | 351 |
| European (non-Finnish)grpmax | 0.242% | 413 |
| Ashkenazi Jewishnot grpmax-eligible | 0.142% | 705 |
| Admixed American | 0.0983% | 1,017 |
| African / African-American | 0.04% | 2,502 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0132% | 7,591 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- HRAS
- Protein
- p.Asp119=
- Coding
- c.357C>T
- MANE Select
- NM_005343
- dbSNP
- rs111352454
- Type
- single nucleotide variant
- Location
- chr11:533546 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 119
- a binding site
Disease context
RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: urinary bladder cancernevus, epidermallinear nevus sebaceous syndromethyroid cancer, nonmedullary, 2Costello syndromehereditary neoplastic syndromeNoonan syndrome and Noonan-related syndromelarge congenital melanocytic nevus
Similar variants
- HRAS p.Ala59Thr Likely pathogenic ★★★ same condition
- HRAS p.Gly12Ser Pathogenic ★★★ same condition
- HRAS p.Gly13Cys Pathogenic ★★★ same condition
- HRAS p.Lys117Arg Pathogenic ★★★ same condition
- HRAS p.Thr58Ile Pathogenic ★★★ same condition
- HRAS p.Gly138Ser Uncertain significance ★★★ ⚠ same condition
- HRAS p.Ile93Val Uncertain significance ★★★ ⚠ same condition
- HRAS p.Lys170Ter 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/hras-p-asp119 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown