Is EXT2 p.Val319fs (c.956_957del) pathogenic?

EXT2 p.Val319fs (c.956957del) is classified Pathogenic in EXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). No gnomAD frequency available for this variant; Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.Val319fs (c.956_957del)?

EXT2 p.Val319fs (c.956_957del) is associated with exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Val319fs (c.956_957del) in the general population?

EXT2 p.Val319fs (c.956_957del) 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.Val319fs

c.956_957del · rs1590570665 · VCV640236

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 2.1	GERP -0.19, 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.Val319fs
Coding: c.956_957del
MANE Select: NM_207122
dbSNP: rs1590570665
Type: Microsatellite
Location: chr11:44126828 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB
Residue 319: a β-strand

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.Val319Ala Uncertain significance ★ ⚠ same residue
EXT2 p.Val319Met Uncertain significance ★ ⚠ same residue
EXT2 p.Ala422fs Pathogenic ★★ same condition
EXT2 p.Ser121fs Pathogenic ★★ same condition
EXT2 p.Val154fs Pathogenic ★★ same condition
EXT2 p.Arg390fs Pathogenic ★ same condition
EXT2 p.Leu261fs Pathogenic ★ same condition
EXT2 p.Leu83fs 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-val319fs (accessed [today's date]).

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