Is EXT1 p.Pro669fs (c.2004del) pathogenic?

EXT1 p.Pro669fs (c.2004del) is classified Pathogenic in EXT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with EXT1 p.Pro669fs (c.2004del)?

EXT1 p.Pro669fs (c.2004del) is associated with Inborn genetic diseases, hereditary multiple osteochondromas (ClinVar).

How common is EXT1 p.Pro669fs (c.2004del) in the general population?

EXT1 p.Pro669fs (c.2004del) is no gnomAD frequency available for this variant (gnomAD).

EXT1 p.Pro669fs

c.2004del · rs1563872934 · VCV581676

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 10 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, 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: EXT1
Protein: p.Pro669fs
Coding: c.2004del
MANE Select: NM_000127
dbSNP: rs1563872934
Type: Deletion
Location: chr8:117804773 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 6 PDB

Full EXT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary multiple osteochondromas

Similar variants

EXT1 p.Ala594fs Pathogenic/Likely pathogenic ★★ same condition
EXT1 p.Arg405fs Pathogenic ★★ same condition
EXT1 p.Gln508fs Pathogenic ★★ same condition
EXT1 p.Glu39fs Pathogenic ★★ same condition
EXT1 p.Leu490fs Pathogenic ★★ same condition
EXT1 p.Phe154fs Pathogenic/Likely pathogenic ★★ same condition
EXT1 p.Phe209fs Likely pathogenic ★★ same condition
EXT1 p.Phe250_Leu251insTer 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/ext1-p-pro669fs (accessed [today's date]).

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