HRAS p.Ala146=
c.438C>A · rs1851236604 · VCV1107363
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Costello syndrome
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 3.8 | GERP 0.64, phastCons 1 |
| Overall | ||
| CADD | 6.221 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HRAS
- Protein
- p.Ala146=
- Coding
- c.438C>A
- MANE Select
- NM_005343
- dbSNP
- rs1851236604
- Type
- single nucleotide variant
- Location
- chr11:533465 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 146
- a binding site; a UniProt-annotated variant site (in cstlo); a turn
Similar variants
- HRAS p.Ala146Val Likely pathogenic ★★ same residue
- HRAS p.Ala146Thr Pathogenic same residue
- HRAS p.Ala146Pro Likely pathogenic ★ 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
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-ala146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown