Is KRAS p.Val152Phe (c.454G>T) pathogenic?

KRAS p.Val152Phe (c.454G>T) is classified Likely pathogenic in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2011-05-03). Absent from gnomAD v4.1; Associated with Noonan syndrome.

What condition is associated with KRAS p.Val152Phe (c.454G>T)?

KRAS p.Val152Phe (c.454G>T) is associated with Noonan syndrome (ClinVar).

How common is KRAS p.Val152Phe (c.454G>T) in the general population?

KRAS p.Val152Phe (c.454G>T) is absent from gnomAD v4.1 (gnomAD).

KRAS p.Val152Phe

c.454G>T · rs397517041 · VCV45126

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Noonan syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.839	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 0.056 · regional, not allelic
Overall
CADD	28.5	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.Val152Phe
Coding: c.454G>T
MANE Select: NM_004985
dbSNP: rs397517041
Type: single nucleotide variant
Location: chr12:25209908 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 152: an α-helix; a UniProt-annotated variant site (in ns3)

Full KRAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Noonan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRAS p.Val152= Likely benign ★★ same residue
KRAS p.Val152Ile Likely pathogenic ★ 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.Thr58Ile Pathogenic ★★★ same condition
KRAS p.Val14Ile 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-val152phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown