HRAS p.Lys104=
c.312G>A · rs1060504682 · VCV415887
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
2
Cardiovascular phenotype
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 0.99 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 5.496 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,028 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000274%
4/1,461,540 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,014 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 8.47e-05% | 1,179,990 |
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.Lys104=
- Coding
- c.312G>A
- MANE Select
- NM_005343
- dbSNP
- rs1060504682
- Type
- single nucleotide variant
- Location
- chr11:533591 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 104
- an α-helix
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-lys104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown