Is EBP p.Arg63Gln (c.188G>A) pathogenic?

EBP p.Arg63Gln (c.188G>A) is classified Conflicting classifications of pathogenicity in EBP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1339); Very rare (popmax 0.00927%, nfe); Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Arg63Gln (c.188G>A)?

EBP p.Arg63Gln (c.188G>A) is associated with X-linked chondrodysplasia punctata 2, MEND syndrome (ClinVar).

How common is EBP p.Arg63Gln (c.188G>A) in the general population?

EBP p.Arg63Gln (c.188G>A) is very rare (popmax 0.00927%, nfe) (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.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

EBP p.Arg63Gln

c.188G>A · rs782638360 · VCV811902

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00927%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -10.20	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 1, phastCons 1
Overall
CADD	29.2	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 0.00927% European (non-Finnish) · 83/895,063 alleles

Filtering AF 0.00764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00702%

Overall 0.00736% 89/1,209,167 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0126%	7,931
European (non-Finnish)grpmax	0.00927%	10,784

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg63Gln
Coding: c.188G>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs782638360
Type: single nucleotide variant
Location: chrX:48523959 (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

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.Arg63Ter 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
EBP p.Gly161Arg 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-arg63gln (accessed [today's date]).

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