Is KRAS p.Val8= (c.24A>G) pathogenic?

KRAS p.Val8= (c.24A>G) is classified Likely benign in KRAS (ClinVar, Expert panel, 16 submitters; last evaluated 2017-04-18). Ultra-rare (popmax 0.0604%, nfe); Associated with RASopathy.

What condition is associated with KRAS p.Val8= (c.24A>G)?

KRAS p.Val8= (c.24A>G) is associated with RASopathy, gastric cancer, urinary bladder cancer (ClinVar).

How common is KRAS p.Val8= (c.24A>G) in the general population?

KRAS p.Val8= (c.24A>G) is ultra-rare (popmax 0.0604%, nfe) (gnomAD).

KRAS p.Val8=

c.24A>G · rs147406419 · VCV45119

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, nfe)

Conditions

RASopathy

ClinGen expert panel — RASopathy VCEP

Likely Benign for RASopathy. Applied ACMG criteria (verbatim):

BS1

Curation rationale (ClinGen, verbatim)

The filtering allele frequency of the c.24A>G (p.Val8=) variant in the KRAS gene is 0.0499% (35/51828) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 2.4	GERP -0.52, phastCons 1
Overall
CADD	9.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0604% European (non-Finnish) · 712/1,179,132 alleles

Filtering AF 0.0566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0552%

Overall 0.046% 742/1,612,464 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0604%	1,656
Remaining individualsnot grpmax-eligible	0.0369%	2,713
African / African-American	0.00667%	14,986
Admixed American	0.00167%	59,894
Finnishnot grpmax-eligible	0.00156%	63,990

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.Val8=
Coding: c.24A>G
MANE Select: NM_004985
dbSNP: rs147406419
Type: single nucleotide variant
Location: chr12:25245361 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 8: a β-strand

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

Also linked: gastric cancer urinary bladder cancer exocrine pancreatic carcinoma arteriovenous malformations of the brain linear nevus sebaceous syndrome lung cancer Toriello-Lacassie-Droste syndrome Noonan syndrome 3 autoimmune lymphoproliferative syndrome type 4 cardiofaciocutaneous syndrome 2 hereditary breast carcinoma acute myeloid leukemia

Similar variants

KRAS p.Val8Ile 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
KRAS p.Pro34Leu Pathogenic ★★★ same condition
KRAS p.Ser65Ile Likely pathogenic ★★★ same condition
KRAS p.Thr58Ile 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-val8 (accessed [today's date]).

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