Is KRAS p.Asp30= (c.90C>T) pathogenic?

KRAS p.Asp30= (c.90C>T) is classified Likely benign in KRAS (ClinVar, Expert panel, 8 submitters; last evaluated 2017-04-18). Ultra-rare (popmax 0.0661%, mid); Associated with RASopathy.

What condition is associated with KRAS p.Asp30= (c.90C>T)?

KRAS p.Asp30= (c.90C>T) is associated with RASopathy, gastric cancer, urinary bladder cancer (ClinVar).

How common is KRAS p.Asp30= (c.90C>T) in the general population?

KRAS p.Asp30= (c.90C>T) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

KRAS p.Asp30=

c.90C>T · rs113623140 · VCV138061

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

Conditions

RASopathy

ClinGen expert panel — RASopathy VCEP

Likely Benign for RASopathy. Applied ACMG criteria (verbatim):

BS1

Curation rationale (ClinGen, verbatim)

The filtering allele frequency of the c.90C>T (p.Asp30=) variant in the KRAS gene is 0.0292% (5/6746) of East Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 2	GERP -3.8, phastCons 1
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0661% Middle Eastern · 4/6,056 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.0119% 192/1,610,502 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.136%	737
Middle Easterngrpmax	0.0661%	1,514
East Asian	0.0513%	1,948
Remaining individualsnot grpmax-eligible	0.0225%	4,453
Admixed American	0.0201%	4,984
South Asian	0.00774%	12,919
European (non-Finnish)	0.00722%	13,858
African / African-American	0.00667%	14,983
Finnishnot grpmax-eligible	0.00313%	31,929

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KRAS
Protein: p.Asp30=
Coding: c.90C>T
MANE Select: NM_004985 · reported on NM_033360
dbSNP: rs113623140
Type: single nucleotide variant
Location: chr12:25245295 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 30: a binding site; a β-strand

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

Disease context

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

Also linked: gastric cancer urinary bladder cancer exocrine pancreatic carcinoma arteriovenous malformations of the brain linear nevus sebaceous syndrome lung cancer Toriello-Lacassie-Droste syndrome prostate cancer, hereditary, 1 Noonan syndrome 3 autoimmune lymphoproliferative syndrome type 4 cardiofaciocutaneous syndrome 2 hereditary breast carcinoma acute myeloid leukemia

Similar variants

KRAS p.Asp30Glu Uncertain significance ⚠ same residue
KRAS p.Asp153Val Pathogenic ★★★ same condition
KRAS p.Gln22Arg Pathogenic ★★★ same condition
KRAS p.Gly60Arg Pathogenic ★★★ same condition
KRAS p.Lys5Asn Pathogenic ★★★ same condition
KRAS p.Pro34Leu Pathogenic ★★★ same condition
KRAS p.Ser65Ile Likely pathogenic ★★★ same condition
KRAS p.Thr58Ile 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-asp30 (accessed [today's date]).

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