Is KRAS p.Gln99= (c.297A>G) pathogenic?

KRAS p.Gln99= (c.297A>G) is classified Likely benign in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). Very rare (popmax 0.00017%, nfe); Associated with RASopathy.

What condition is associated with KRAS p.Gln99= (c.297A>G)?

KRAS p.Gln99= (c.297A>G) is associated with RASopathy (ClinVar).

How common is KRAS p.Gln99= (c.297A>G) in the general population?

KRAS p.Gln99= (c.297A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

KRAS p.Gln99=

c.297A>G · VCV3681099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.9	GERP -0.47, phastCons 1
Overall
CADD	15.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,274 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,248 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.Gln99=
Coding: c.297A>G
MANE Select: NM_004985
Type: single nucleotide variant
Location: chr12:25225767 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 99: an α-helix

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.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
KRAS p.Val14Ile 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-gln99 (accessed [today's date]).

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