Is KRAS p.Gln22Pro (c.65A>C) pathogenic?

KRAS p.Gln22Pro (c.65A>C) is classified Uncertain significance in KRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with KRAS p.Gln22Pro (c.65A>C)?

KRAS p.Gln22Pro (c.65A>C) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is KRAS p.Gln22Pro (c.65A>C) in the general population?

KRAS p.Gln22Pro (c.65A>C) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KRAS p.Gln22Pro (c.65A>C)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

KRAS p.Gln22Pro

c.65A>C · rs727503110 · VCV1711025

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -12.74	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Gln22Pro
Coding: c.65A>C
MANE Select: NM_004985
dbSNP: rs727503110
Type: single nucleotide variant
Location: chr12:25245320 (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

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

KRAS p.Gln22Arg Pathogenic ★★★ same residue
KRAS p.Gln22Glu Pathogenic ★★ same residue
KRAS p.Gln22Lys Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Gln22= Likely benign ★★ same residue
KRAS p.Gln22Leu Likely pathogenic ★ same residue
KRAS p.Asp30= Likely benign ★★★ same condition
KRAS p.Lys5Glu Pathogenic/Likely pathogenic ★★ same condition
KRAS c.111+16A>G Likely benign ★ 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-gln22pro (accessed [today's date]).

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