Is PTPN11 p.Lys89fs (c.265_269del) pathogenic?

PTPN11 p.Lys89fs (c.265269del) is classified Pathogenic/Likely pathogenic in PTPN11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-30). No gnomAD frequency available for this variant; Associated with PTPN11-related disorder.

What condition is associated with PTPN11 p.Lys89fs (c.265_269del)?

PTPN11 p.Lys89fs (c.265_269del) is associated with PTPN11-related disorder, metachondromatosis, RASopathy (ClinVar).

How common is PTPN11 p.Lys89fs (c.265_269del) in the general population?

PTPN11 p.Lys89fs (c.265_269del) is no gnomAD frequency available for this variant (gnomAD).

PTPN11 p.Lys89fs

c.265_269del · rs2540416086 · VCV981580

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

PTPN11-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTPN11
Protein: p.Lys89fs
Coding: c.265_269del
MANE Select: NM_002834
dbSNP: rs2540416086
Type: Deletion
Location: chr12:112450444 (GRCh38)
Gene constraint: LOEUF 0.156 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.34 · 117 PDB
Residue 89: the sh2 1 domain; a β-strand

Full PTPN11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PTPN11-related disorder

Also linked: metachondromatosis RASopathy

Similar variants

PTPN11 p.Arg220_Ile221insTer Pathogenic ★★ same condition
PTPN11 p.Gly60del Pathogenic/Likely pathogenic ★★ same condition
PTPN11 p.Val243_Lys244del Uncertain significance ★★ same condition
PTPN11 p.Asp296fs Pathogenic ★ same condition
PTPN11 p.Asp473fs Pathogenic ★ same condition
PTPN11 p.Gln57_Asn58delinsHis Likely pathogenic ★ same condition
PTPN11 p.Leu212fs Pathogenic ★ same condition
PTPN11 p.Thr357fs Likely 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/ptpn11-p-lys89fs (accessed [today's date]).

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