Is KRAS p.Val152= (c.456T>G) pathogenic?

KRAS p.Val152= (c.456T>G) is classified Likely benign in KRAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-13). Very rare (popmax 0.00221%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with KRAS p.Val152= (c.456T>G)?

KRAS p.Val152= (c.456T>G) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is KRAS p.Val152= (c.456T>G) in the general population?

KRAS p.Val152= (c.456T>G) is very rare (popmax 0.00221%, nfe) (gnomAD).

KRAS p.Val152=

c.456T>G · rs767947451 · VCV1239850

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Conditions

Cardiovascular phenotype

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 5.1	GERP 0.33, phastCons 1
Overall
CADD	8.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,175,278 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00131%

Overall 0.00162% 26/1,607,450 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.Val152=
Coding: c.456T>G
MANE Select: NM_004985
dbSNP: rs767947451
Type: single nucleotide variant
Location: chr12:25209906 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RASopathy

Similar variants

KRAS p.Val152Ile Likely pathogenic ★ same residue
KRAS p.Val152Phe Likely pathogenic ★ same residue
KRAS p.Asp153Val Pathogenic ★★★ same condition
KRAS p.Gln22Arg Pathogenic ★★★ same condition
KRAS p.Gly60Arg Pathogenic ★★★ same condition
KRAS p.Lys5Asn 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-val152 (accessed [today's date]).

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