Is KRAS p.Thr87= (c.261T>G) pathogenic?

KRAS p.Thr87= (c.261T>G) is classified Likely benign in KRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-30). Ultra-rare (popmax 0.0165%, mid); Associated with RASopathy.

What condition is associated with KRAS p.Thr87= (c.261T>G)?

KRAS p.Thr87= (c.261T>G) is associated with RASopathy (ClinVar).

How common is KRAS p.Thr87= (c.261T>G) in the general population?

KRAS p.Thr87= (c.261T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

KRAS p.Thr87=

c.261T>G · rs1565884900 · VCV2994655

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 9.4	GERP 0.64, phastCons 1
Overall
CADD	11.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000137% 2/1,461,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
European (non-Finnish)	8.48e-05%	1,179,389

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.Thr87=
Coding: c.261T>G
MANE Select: NM_004985
dbSNP: rs1565884900
Type: single nucleotide variant
Location: chr12:25227263 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 87: 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.Thr87Ala 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-thr87 (accessed [today's date]).

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