Is KRAS p.Val8fs (c.21_22insT) pathogenic?

KRAS p.Val8fs (c.2122insT) is classified Uncertain significance in KRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). Absent from gnomAD; Associated with prostate cancer, hereditary, 1.

What condition is associated with KRAS p.Val8fs (c.21_22insT)?

KRAS p.Val8fs (c.21_22insT) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is KRAS p.Val8fs (c.21_22insT) in the general population?

KRAS p.Val8fs (c.21_22insT) is absent from gnomAD (gnomAD).

How is Familial prostate cancer inherited?

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

KRAS p.Val8fs

c.21_22insT · rs2548933381 · VCV1711009

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val8fs
Coding: c.21_22insT
MANE Select: NM_004985
dbSNP: rs2548933381
Type: Insertion
Location: chr12:25245363 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 8: a β-strand

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.Val8= Likely benign ★★★ same residue
KRAS c.-11-8_-11-7insC Uncertain significance same condition
KRAS p.Ala11fs Uncertain significance same condition
KRAS p.Val8Ile Uncertain significance same residue
KRAS p.Val9_Gly10insLeu Uncertain significance same condition
KRAS p.Asp30= Likely benign ★★★ same condition
KRAS p.Lys5Glu Pathogenic/Likely pathogenic ★★ same condition
KRAS c.111+14del 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-val8fs (accessed [today's date]).

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