Is KRAS p.Lys147Arg (c.440A>G) pathogenic?

KRAS p.Lys147Arg (c.440A>G) is classified Pathogenic in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). AlphaMissense: likely benign (0.2383); Absent from gnomAD v4.1; Associated with Noonan syndrome 3.

What condition is associated with KRAS p.Lys147Arg (c.440A>G)?

KRAS p.Lys147Arg (c.440A>G) is associated with Noonan syndrome 3 (ClinVar).

How common is KRAS p.Lys147Arg (c.440A>G) in the general population?

KRAS p.Lys147Arg (c.440A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRAS p.Lys147Arg (c.440A>G)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

KRAS p.Lys147Arg

c.440A>G · rs1135401776 · VCV431103

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan syndrome 3

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign ⚠ discordant with ClinVar
REVEL	0.686	pathogenic-leaning
SaProt	LLR -6.93	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRAS
Protein: p.Lys147Arg
Coding: c.440A>G
MANE Select: NM_004985 · reported on NM_033360
dbSNP: rs1135401776
Type: single nucleotide variant
Location: chr12:25225624 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 147: a binding site; a UniProt-annotated variant site (in cfc2); a turn

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

Disease context

Noonan syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRAS p.Lys147Met Likely pathogenic ★ same residue
KRAS p.Lys147Glu Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Lys147Asn Likely pathogenic ★ same residue
KRAS p.Asp153Val Pathogenic ★★★ same condition
KRAS p.Gln22Arg Pathogenic ★★★ same condition
KRAS p.Gly60Arg Pathogenic ★★★ same condition
KRAS p.Pro34Leu Pathogenic ★★★ same condition
KRAS p.Ser65Ile 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-lys147arg (accessed [today's date]).

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