Is KRAS p.Asp33= (c.99T>C) pathogenic?

KRAS p.Asp33= (c.99T>C) is classified Uncertain significance in KRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with KRAS p.Asp33= (c.99T>C)?

KRAS p.Asp33= (c.99T>C) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is KRAS p.Asp33= (c.99T>C) in the general population?

KRAS p.Asp33= (c.99T>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.

KRAS p.Asp33=

c.99T>C · rs2135805765 · VCV1711041

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.016	GERP -3.8, phastCons 0.018
Overall
CADD	6.464	PHRED · no single calibrated threshold — expert panels disagree

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.Asp33=
Coding: c.99T>C
MANE Select: NM_004985
dbSNP: rs2135805765
Type: single nucleotide variant
Location: chr12:25245286 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB

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.Asp33Gly Uncertain significance ★★ ⚠ 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
KRAS p.Gln25= Likely benign ★ same condition
KRAS c.111+11T>C Uncertain significance same condition
KRAS c.111+1G>C Uncertain significance same condition
KRAS c.111+24A>G Uncertain significance 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-asp33 (accessed [today's date]).

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