KRAS p.Gln22=
c.66G>A · rs1951663491 · VCV2195758
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
RASopathy
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 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 13.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,266 alleles
Overall
0.000657%
1/152,190 alleles · very rare
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
- KRAS
- Protein
- p.Gln22=
- Coding
- c.66G>A
- MANE Select
- NM_004985
- dbSNP
- rs1951663491
- Type
- single nucleotide variant
- Location
- chr12:25245319 (GRCh38)
- Gene constraint
- LOEUF 0.264 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.65 · 549 PDB
- Residue 22
- a UniProt-annotated variant site (in cfc2; exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired gtpase-activating protein-stimulated gtp hydrolysis but functional in interaction with effectors); a UniProt-annotated variant site (in ns3; impairs gtpase-activating protein stimulated gtp hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction); an α-helix
Similar variants
- KRAS p.Gln22Arg Pathogenic ★★★ same residue
- KRAS p.Gln22Glu Pathogenic ★★ same residue
- KRAS p.Gln22Lys Pathogenic/Likely pathogenic ★★ same residue
- KRAS p.Gln22Leu Likely pathogenic ★ same residue
- KRAS p.Gln22Pro Uncertain significance ⚠ same residue
- KRAS p.Asp153Val Pathogenic ★★★ same condition
- KRAS p.Gly60Arg Pathogenic ★★★ same condition
- KRAS p.Lys5Asn 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/kras-p-gln22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown