Is EBP p.Arg62Trp (c.184C>T) pathogenic?

EBP p.Arg62Trp (c.184C>T) is classified Pathogenic/Likely pathogenic in EBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-24). AlphaMissense: likely benign (0.2766); Very rare (popmax 0.00176%, sas); Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Arg62Trp (c.184C>T)?

EBP p.Arg62Trp (c.184C>T) is associated with X-linked chondrodysplasia punctata 2 (ClinVar).

How common is EBP p.Arg62Trp (c.184C>T) in the general population?

EBP p.Arg62Trp (c.184C>T) is very rare (popmax 0.00176%, sas) (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.Arg62Trp (c.184C>T)?

AlphaMissense predicts likely benign (score 0.2766) — an in-silico prediction, not a clinical call.

EBP p.Arg62Trp

c.184C>T · rs372974717 · VCV1410474

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
AlphaMissense	0.2766	likely benign ⚠ discordant with ClinVar
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -6.59	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.4	GERP 0.87, phastCons 1
Overall
CADD	28.2	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

Grpmax group 0.00176% South Asian · 1/56,957 alleles

Overall 9.11e-05% 1/1,098,172 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: EBP
Protein: p.Arg62Trp
Coding: c.184C>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs372974717
Type: single nucleotide variant
Location: chrX:48523955 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 62: 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.Arg62Gln Uncertain significance ★★ ⚠ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same condition
EBP p.Arg110Ter Pathogenic ★★ same condition
EBP p.Arg147His Pathogenic ★★ ⚠ same condition
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same condition
EBP p.Gly161Arg Likely pathogenic ★★ same condition
EBP p.Trp186Ter Pathogenic ★★ same condition
EBP p.Trp61Ter 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-arg62trp (accessed [today's date]).

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