HRAS p.Lys170=
c.510G>A · rs397517143 · VCV45305
ClinGen expert panel — RASopathy VCEP
Likely Benign for RASopathy. Applied ACMG criteria (verbatim):
BS1 BP5 BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.510G>A variant in the HRAS gene is a synonymous (silent) variant (p.Lys170=) at a nucleotide that is not predicted by SpliceAI to impact splicing (BP4, BP7). The filtering allele frequency in gnomAD v4.1.0 is 0.02525% (17/44900 alleles) in the East Asian population meeting BS1. This variant has been identified in patients with an alternate molecular basis for disease (BP5; LMM and GeneDx internal data; GTR ID's: 21766, 26957; ClinVar SCV000062144.5; SCV000168832.9). In summary, this variant meets criteria to be classified as likely benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BS1, BP4, BP5, BP7 (Specification Version 2.1, 09/17/2024)
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 2.1 | GERP 5.2, phastCons 1 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,641 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,822 |
| South Asian | 0.00439% | 22,773 |
| Admixed American | 0.00167% | 60,016 |
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
- HRAS
- Protein
- p.Lys170=
- Coding
- c.510G>A
- MANE Select
- NM_005343
- dbSNP
- rs397517143
- Type
- single nucleotide variant
- Location
- chr11:532696 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 170
- a cross-link site; the 'hypervariable region' region
Disease context
RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Costello syndrome
Similar variants
- HRAS p.Lys170Ter Uncertain significance ★★★ same residue
- HRAS p.Lys170Arg Uncertain significance ★ ⚠ same residue
- 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
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-lys170 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown