Is KRAS p.Met188Val (c.562A>G) pathogenic?

KRAS p.Met188Val (c.562A>G) is classified Uncertain significance in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). Very rare (popmax 0.00447%, eas); Associated with RASopathy.

What condition is associated with KRAS p.Met188Val (c.562A>G)?

KRAS p.Met188Val (c.562A>G) is associated with RASopathy (ClinVar).

How common is KRAS p.Met188Val (c.562A>G) in the general population?

KRAS p.Met188Val (c.562A>G) is very rare (popmax 0.00447%, eas) (gnomAD).

KRAS p.Met188Val

c.562A>G · VCV4801158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.449	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 0.056 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,724 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000124% 2/1,607,796 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.Met188Val
Coding: c.562A>G
MANE Select: NM_004985
Type: single nucleotide variant
Location: chr12:25209800 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB

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

Disease context

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

Similar variants

KRAS p.Met188Ile Uncertain significance ★ same residue
KRAS p.Met188Thr Uncertain significance ★ same residue
KRAS p.Ile188Lys Uncertain significance ★ same residue
KRAS p.Met188Arg Uncertain significance ★ 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

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-met188val (accessed [today's date]).

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