Is KRAS p.Val186= (c.558A>G) pathogenic?

KRAS p.Val186= (c.558A>G) is classified Likely benign in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). Very rare (popmax 0.00134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with KRAS p.Val186= (c.558A>G)?

KRAS p.Val186= (c.558A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is KRAS p.Val186= (c.558A>G) in the general population?

KRAS p.Val186= (c.558A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

KRAS p.Val186=

c.558A>G · VCV3865297

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 0.63, phastCons 1
Overall
CADD	9.276	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,874 alleles

Overall 6.87e-05% 1/1,455,374 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.Val186=
Coding: c.558A>G
MANE Select: NM_004985
Type: single nucleotide variant
Location: chr12:25209804 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 186: a modified residue (cysteine methyl ester)

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

Similar variants

KRAS p.Val186Ile Uncertain significance ★ same residue
KRAS c.451-5565G>A Benign/Likely benign ★★ same condition
KRAS c.451-5617= Benign ★★ same condition
KRAS c.*103A>G Likely benign ★★ same condition
KRAS c.*16T>C Likely benign ★★ same condition
KRAS p.Ala146= Likely benign ★★ same condition
KRAS p.Ala155= Likely benign ★★ same condition
KRAS p.Arg161= Likely benign ★★ 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-val186 (accessed [today's date]).

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