Is EBP p.Ala54fs (c.159del) pathogenic?

EBP p.Ala54fs (c.159del) is classified Likely pathogenic in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Ala54fs (c.159del)?

EBP p.Ala54fs (c.159del) is associated with X-linked chondrodysplasia punctata 2 (ClinVar).

How is X-linked dominant chondrodysplasia punctata inherited?

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

EBP p.Ala54fs

c.159del · VCV4293428

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

X-linked chondrodysplasia punctata 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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.24	GERP 2, phastCons 0.056

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

Variant & gene context

Gene: EBP
Protein: p.Ala54fs
Coding: c.159del
MANE Select: NM_001378122 · reported on NM_006579
Type: Deletion
Location: chrX:48523930 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 54: the 'disordered' region

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

Disease context

X-linked chondrodysplasia punctata 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked dominant chondrodysplasia punctata (Orphanet):

Inheritance: X-linked dominant
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

EBP p.Ala54Val Uncertain significance ★★ ⚠ same residue
EBP p.Ser98fs Pathogenic ★ same condition
EBP p.Ala54= Likely benign ★ same residue
EBP p.Pro131fs Pathogenic same condition
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same condition
EBP p.Arg110Ter Pathogenic ★★ same condition
EBP p.Arg147His Pathogenic ★★ ⚠ same condition
EBP p.Arg62Trp 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/ebp-p-ala54fs (accessed [today's date]).

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