Is KRAS p.Gln22Lys (c.64C>A) pathogenic?

KRAS p.Gln22Lys (c.64C>A) is classified Pathogenic/Likely pathogenic in KRAS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-02-16). AlphaMissense: likely pathogenic (0.9799); Absent from gnomAD v4.1; Associated with KRAS-related disorder.

What condition is associated with KRAS p.Gln22Lys (c.64C>A)?

KRAS p.Gln22Lys (c.64C>A) is associated with KRAS-related disorder, linear nevus sebaceous syndrome, RASopathy (ClinVar).

How common is KRAS p.Gln22Lys (c.64C>A) in the general population?

KRAS p.Gln22Lys (c.64C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRAS p.Gln22Lys (c.64C>A)?

AlphaMissense predicts likely pathogenic (score 0.9799) — an in-silico prediction, not a clinical call.

KRAS p.Gln22Lys

c.64C>A · rs121913236 · VCV376325

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9799 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,818)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KRAS-related disorder

Computational evidence

Protein change
AlphaMissense	0.9799	likely pathogenic ✓ concordant with ClinVar
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	28.6	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

No allele count reported in gnomAD v4.1 (AN 1,612,818). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KRAS
Protein: p.Gln22Lys
Coding: c.64C>A
MANE Select: NM_004985 · reported on NM_033360
dbSNP: rs121913236
Type: single nucleotide variant
Location: chr12:25245321 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 22: a UniProt-annotated variant site (in cfc2; exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired gtpase-activating protein-stimulated gtp hydrolysis but functional in interaction with effectors); a UniProt-annotated variant site (in ns3; impairs gtpase-activating protein stimulated gtp hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction); an α-helix

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

Disease context

KRAS-related disorder

Also linked: linear nevus sebaceous syndrome RASopathy vascular malformation

Similar variants

KRAS p.Gln22Arg Pathogenic ★★★ same residue
KRAS p.Gln22Glu Pathogenic ★★ same residue
KRAS p.Gln22= Likely benign ★★ same residue
KRAS p.Gln22Leu Likely pathogenic ★ same residue
KRAS p.Gln22Pro Uncertain significance ⚠ same residue
KRAS p.Asp153Val 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-gln22lys (accessed [today's date]).

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