Is EBP p.Arg63Ter (c.187C>T) pathogenic?

EBP p.Arg63Ter (c.187C>T) is classified Pathogenic in EBP (ClinVar, Single submitter, 4 submitters; last evaluated 2020-12-21). Absent from gnomAD v4.1; Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Arg63Ter (c.187C>T)?

EBP p.Arg63Ter (c.187C>T) is associated with X-linked chondrodysplasia punctata 2 (ClinVar).

How common is EBP p.Arg63Ter (c.187C>T) in the general population?

EBP p.Arg63Ter (c.187C>T) is absent from gnomAD v4.1 (gnomAD).

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.Arg63Ter

c.187C>T · rs104894799 · VCV11484

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	Δ0.53	acceptor gain · deltas
Pangolin	Δ0.50	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.2	GERP -0.064, phastCons 0.95
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EBP
Protein: p.Arg63Ter
Coding: c.187C>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs104894799
Type: single nucleotide variant
Location: chrX:48523958 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 63: 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.Arg63Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
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
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same condition
EBP p.Gly161Arg Likely pathogenic ★★ same condition
EBP p.Trp186Ter 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-arg63ter (accessed [today's date]).

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