KRAS p.Phe156Ile
c.466T>A · rs397517042 · VCV163758
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
3
Noonan syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.896 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.79 | unconstrained · MANE · 16 kb · p 0.056 · regional, not allelic |
| Overall | ||
| CADD | 27.7 | 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
- KRAS
- Protein
- p.Phe156Ile
- Coding
- c.466T>A
- MANE Select
- NM_004985
- dbSNP
- rs397517042
- Type
- single nucleotide variant
- Location
- chr12:25209896 (GRCh38)
- Gene constraint
- LOEUF 0.264 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.65 · 549 PDB
- Residue 156
- an α-helix; a UniProt-annotated variant site (in ns3; the patient also has features of cardiofaciocutaneous syndrome); a UniProt-annotated variant site (found in a patient with costello syndrome; 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)
Similar variants
- KRAS p.Phe156Val Pathogenic/Likely pathogenic ★★ same residue
- KRAS p.Phe156Ser Pathogenic ★ same residue
- KRAS p.Phe156= Likely benign ★ same residue
- KRAS p.Asp153Val Pathogenic ★★★ same condition
- KRAS p.Gln22Arg Pathogenic ★★★ same condition
- KRAS p.Gly60Arg Pathogenic ★★★ same condition
- KRAS p.Pro34Leu Pathogenic ★★★ same condition
- KRAS p.Ser65Ile Likely 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-phe156ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown