Is EBP p.Val84Ile (c.250G>A) pathogenic?

EBP p.Val84Ile (c.250G>A) is classified Conflicting classifications of pathogenicity in EBP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0178%, eas); Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Val84Ile (c.250G>A)?

EBP p.Val84Ile (c.250G>A) is associated with X-linked chondrodysplasia punctata 2, MEND syndrome (ClinVar).

How common is EBP p.Val84Ile (c.250G>A) in the general population?

EBP p.Val84Ile (c.250G>A) is ultra-rare (popmax 0.0178%, eas) (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.Val84Ile (c.250G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

EBP p.Val84Ile

c.250G>A · rs1335777232 · VCV3086881

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.038	GERP -4.1
Overall
CADD	1.689	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 0.0178% East Asian · 6/33,773 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.00215% 26/1,209,373 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,629
European (non-Finnish)	0.00212%	47,115
African / African-American	0.00176%	56,934

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.Val84Ile
Coding: c.250G>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs1335777232
Type: single nucleotide variant
Location: chrX:48524021 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 84: 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.Val84Leu Uncertain significance ★ ⚠ 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-val84ile (accessed [today's date]).

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