Is KRAS p.Lys88= (c.264A>G) pathogenic?

KRAS p.Lys88= (c.264A>G) is classified Benign/Likely benign in KRAS (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0846%, sas); Associated with RASopathy.

What condition is associated with KRAS p.Lys88= (c.264A>G)?

KRAS p.Lys88= (c.264A>G) is associated with RASopathy (ClinVar).

How common is KRAS p.Lys88= (c.264A>G) in the general population?

KRAS p.Lys88= (c.264A>G) is ultra-rare (popmax 0.0846%, sas) (gnomAD).

KRAS p.Lys88=

c.264A>G · rs370920665 · VCV227471

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

Conditions

RASopathy

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 -1.6	GERP -3.8
Overall
CADD	6.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,070 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.0158% 255/1,613,344 alleles · ultra-rare exomes 221/1,461,134 · genomes 34/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,183
Admixed American	0.0583%	1,714
Remaining individualsnot grpmax-eligible	0.0176%	5,678
Middle Eastern	0.0164%	6,082
European (non-Finnish)	0.0107%	9,361
African / African-American	0.00667%	14,984

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.Lys88=
Coding: c.264A>G
MANE Select: NM_004985
dbSNP: rs370920665
Type: single nucleotide variant
Location: chr12:25227260 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 88: an α-helix

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

Similar variants

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
KRAS p.Val14Ile 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-lys88 (accessed [today's date]).

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