HRAS p.Pro167Leu
c.500C>T · rs730880457 · VCV40444
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00447%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.166 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.98 | GERP -0.32, phastCons 0.42 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 1,164 bp · p 0.94 · regional, not allelic |
| Overall | ||
| CADD | 17.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00447%
East Asian · 2/44,734 alleles
Filtering AF
0.00232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00275%
44/1,600,406 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00447% | 22,367 |
| African / African-American | 0.00401% | 24,933 |
| European (non-Finnish) | 0.00314% | 31,847 |
| Admixed American | 0.00168% | 59,686 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,168 |
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.Pro167Leu
- Coding
- c.500C>T
- MANE Select
- NM_005343 · reported on NM_176795
- dbSNP
- rs730880457
- Type
- single nucleotide variant
- Location
- chr11:533309 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 167
- the 'hypervariable region' region
Similar variants
- HRAS p.Pro167= Likely benign ★★ same residue
- HRAS p.Lys167Arg Uncertain significance ★ ⚠ same residue
- HRAS p.Pro167fs Uncertain significance ★ same residue
- HRAS p.Ala59Thr Likely pathogenic ★★★ same type
- HRAS p.Gly12Ser Pathogenic ★★★ same type
- HRAS p.Gly13Cys Pathogenic ★★★ same type
- HRAS p.Lys117Arg Pathogenic ★★★ same type
- HRAS p.Thr58Ile Pathogenic ★★★ same type
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-pro167leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown