HRAS p.Val14=
c.42G>A · rs777038147 · VCV259748
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0227%, afr)
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 2.1 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 10.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0227%
African / African-American · 17/74,912 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.00105%
17/1,613,314 alleles · ultra-rare
exomes 9/1,461,160 · genomes 8/152,154 · joint denominator
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.Val14=
- Coding
- c.42G>A
- MANE Select
- NM_005343
- dbSNP
- rs777038147
- Type
- single nucleotide variant
- Location
- chr11:534281 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.50 · 256 PDB
- Residue 14
- a binding site; a β-strand
Similar variants
- HRAS p.Val14Gly 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
- HRAS p.Ile93Val 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-val14 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown