Is CANT1 p.Asp89fs (c.267del) pathogenic?

CANT1 p.Asp89fs (c.267del) is classified Likely pathogenic in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). Very rare (popmax 8.48e-05%, nfe); Associated with epiphyseal dysplasia, multiple, 7.

What condition is associated with CANT1 p.Asp89fs (c.267del)?

CANT1 p.Asp89fs (c.267del) is associated with epiphyseal dysplasia, multiple, 7, Desbuquois dysplasia 1 (ClinVar).

How common is CANT1 p.Asp89fs (c.267del) in the general population?

CANT1 p.Asp89fs (c.267del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CANT1 p.Asp89fs

c.267del · VCV3583087

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

epiphyseal dysplasia, multiple, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,892 alleles

Overall 6.84e-05% 1/1,461,838 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CANT1
Protein: p.Asp89fs
Coding: c.267del
MANE Select: NM_001159773
Type: Deletion
Location: chr17:78997356 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.47 · 4 PDB

Full CANT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epiphyseal dysplasia, multiple, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Desbuquois dysplasia 1

For Multiple epiphyseal dysplasia type 7 (Orphanet):

Onset: Childhood

Similar variants

CANT1 p.Asp89Val Uncertain significance ★ ⚠ same residue
CANT1 p.Arg63fs Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Pro245fs Pathogenic same condition
CANT1 c.632-5_661dup Likely pathogenic ★★ same condition
CANT1 c.836-9G>A Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Arg300Cys Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Glu116fs Pathogenic ★★ same condition
CANT1 p.Glu215Lys Pathogenic/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/cant1-p-asp89fs (accessed [today's date]).

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