Is EBP p.Trp47Cys (c.141G>T) pathogenic?

EBP p.Trp47Cys (c.141G>T) is classified Pathogenic in EBP (ClinVar, Single submitter, 2 submitters; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.6549); Absent from gnomAD v4.1; Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Trp47Cys (c.141G>T)?

EBP p.Trp47Cys (c.141G>T) is associated with X-linked chondrodysplasia punctata 2, MEND syndrome (ClinVar).

How common is EBP p.Trp47Cys (c.141G>T) in the general population?

EBP p.Trp47Cys (c.141G>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.

What do computational predictors say about EBP p.Trp47Cys (c.141G>T)?

AlphaMissense predicts likely pathogenic (score 0.6549) — an in-silico prediction, not a clinical call.

EBP p.Trp47Cys

c.141G>T · rs587783599 · VCV158530

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6549 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
AlphaMissense	0.6549	likely pathogenic ✓ concordant with ClinVar
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -12.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.64	acceptor loss · deltas
Pangolin	Δ0.63	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Trp47Cys
Coding: c.141G>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs587783599
Type: single nucleotide variant
Location: chrX:48523912 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 47: 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

Also linked: MEND syndrome

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.Trp47Arg Pathogenic same residue
EBP p.Trp47Ter Pathogenic ★ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same condition
EBP p.Arg110Ter Pathogenic ★★ same condition
EBP p.Arg147Cys Pathogenic/Likely 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

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-trp47cys (accessed [today's date]).

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