Is EXT2 p.His88fs (c.264_275delinsAC) pathogenic?

EXT2 p.His88fs (c.264275delinsAC) is classified Pathogenic in EXT2 (ClinVar, Single submitter, 1 submitter). Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.His88fs (c.264_275delinsAC)?

EXT2 p.His88fs (c.264_275delinsAC) is associated with exostoses, multiple, type 2 (ClinVar).

How is Multiple osteochondromas inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

EXT2 p.His88fs

c.264_275delinsAC · VCV3764694

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

exostoses, multiple, type 2

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 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.56	GERP -3.5, phastCons 1

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

Variant & gene context

Gene: EXT2
Protein: p.His88fs
Coding: c.264_275delinsAC
MANE Select: NM_207122
Type: Indel
Location: chr11:44107976 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB
Residue 88: an α-helix

Full EXT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

exostoses, multiple, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple osteochondromas (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: >1 / 1000 (Specific population)

Similar variants

EXT2 p.His88= Benign/Likely benign ★★ same residue
EXT2 p.Phe633Ser Uncertain significance ★★ same condition
EXT2 c.1080-1085_1173+5684delinsGC Pathogenic ★ same condition
EXT2 p.Phe43_Gln44delinsLeuTer Pathogenic ★ same condition
EXT2 p.His601Pro Uncertain significance ★ same condition
EXT2 p.Leu177Ile Uncertain significance ★ same condition
EXT2 c.1079+1G>A Pathogenic ★★ same condition
EXT2 c.1079+1G>T 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/ext2-p-his88fs (accessed [today's date]).

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