Is KRAS p.Gly12= (c.36T>A) pathogenic?

KRAS p.Gly12= (c.36T>A) is classified Likely benign in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-02). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with KRAS p.Gly12= (c.36T>A)?

KRAS p.Gly12= (c.36T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is KRAS p.Gly12= (c.36T>A) in the general population?

KRAS p.Gly12= (c.36T>A) is absent from gnomAD v4.1 (gnomAD).

KRAS p.Gly12=

c.36T>A · rs2548933314 · VCV1734090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 9.3	GERP 0.66, phastCons 1
Overall
CADD	13.31	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.Gly12=
Coding: c.36T>A
MANE Select: NM_004985
dbSNP: rs2548933314
Type: single nucleotide variant
Location: chr12:25245349 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 12: a UniProt-annotated variant site (in colorectal cancer samples; somatic mutation); a UniProt-annotated variant site (in lung carcinoma; somatic mutation; also found in metastatic colorectal cancer); a UniProt-annotated variant site (in gasc, jmml and sfm; somatic mutation; also found in pancreatic carcinoma and lung carcinoma; also found in metastatic colorectal cancer); a UniProt-annotated variant site (in lung cancer and bladder cancer; somatic mutation); a UniProt-annotated variant site (in gasc and jmml; also found in lung carcinoma; somatic mutation); a UniProt-annotated variant site (in gasc; also found in lung carcinoma, pancreatic carcinoma and colon cancer; also found in metastatic colorectal cancer; somatic mutation; it is constitutively activated and stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts; promotes gtp binding); an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRAS p.Gly12Ala Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Gly12Arg Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Gly12Asp Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Gly12Cys Likely pathogenic ★★ same residue
KRAS p.Gly12Ser Pathogenic ★★ same residue
KRAS p.Gly12Val Pathogenic ★★ same residue
KRAS c.451-5565G>A Benign/Likely benign ★★ same condition
KRAS c.451-5617= 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-gly12 (accessed [today's date]).

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