Is EXT2 p.Leu321fs (c.960del) pathogenic?

EXT2 p.Leu321fs (c.960del) is classified Pathogenic in EXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). No gnomAD frequency available for this variant; Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.Leu321fs (c.960del)?

EXT2 p.Leu321fs (c.960del) is associated with exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Leu321fs (c.960del) in the general population?

EXT2 p.Leu321fs (c.960del) is no gnomAD frequency available for this variant (gnomAD).

How is Multiple osteochondromas inherited?

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

EXT2 p.Leu321fs

c.960del · rs1954412043 · VCV941039

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 6 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 2.6, phastCons 1

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: EXT2
Protein: p.Leu321fs
Coding: c.960del
MANE Select: NM_207122
dbSNP: rs1954412043
Type: Deletion
Location: chr11:44126835 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB

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 c.626+2_626+5del Pathogenic ★★ same condition
EXT2 p.Gln382fs Pathogenic ★★ same condition
EXT2 p.Val593fs Likely pathogenic ★★ same condition
EXT2 p.Val68fs Pathogenic ★★ same condition
EXT2 c.2019-2del Uncertain significance ★★ same condition
EXT2 c.1806+9del Benign/Likely benign ★★ same condition
EXT2 c.1080-2del Pathogenic ★ same condition
EXT2 c.1489_1495+12del 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/ext2-p-leu321fs (accessed [today's date]).

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