Is KRAS p.Arg97Lys (c.290G>A) pathogenic?

KRAS p.Arg97Lys (c.290G>A) is classified Likely pathogenic in KRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-08-28). AlphaMissense: ambiguous (0.4248); Very rare (popmax 8.51e-05%, nfe); Associated with non-small cell lung carcinoma.

What condition is associated with KRAS p.Arg97Lys (c.290G>A)?

KRAS p.Arg97Lys (c.290G>A) is associated with non-small cell lung carcinoma (ClinVar).

How common is KRAS p.Arg97Lys (c.290G>A) in the general population?

KRAS p.Arg97Lys (c.290G>A) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about KRAS p.Arg97Lys (c.290G>A)?

AlphaMissense predicts ambiguous (score 0.4248) — an in-silico prediction, not a clinical call.

KRAS p.Arg97Lys

c.290G>A · rs727503106 · VCV163761

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

non-small cell lung carcinoma

Computational evidence

Protein change
AlphaMissense	0.4248	ambiguous
REVEL	0.379	indeterminate
SaProt	LLR -11.76	damaging
Splicing
SpliceAI	Δ0.76	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.76	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,706 alleles

Overall 6.86e-05% 1/1,456,898 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.Arg97Lys
Coding: c.290G>A
MANE Select: NM_004985
dbSNP: rs727503106
Type: single nucleotide variant
Location: chr12:25227234 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 97: an α-helix

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

Disease context

non-small cell lung carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRAS p.Gly12Ala Pathogenic/Likely pathogenic ★★ same condition
KRAS p.Gly12Arg Pathogenic/Likely pathogenic ★★ same condition
KRAS p.Gly12Asp Pathogenic/Likely pathogenic ★★ same condition
KRAS p.Gly12Cys Likely pathogenic ★★ same condition
KRAS p.Gly12Ser Pathogenic ★★ same condition
KRAS p.Gly12Val Pathogenic ★★ same condition
KRAS p.Gly13Asp Pathogenic ★★ same condition
KRAS p.Gly13Cys Pathogenic/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-arg97lys (accessed [today's date]).

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