Is EBP p.Ala95Thr (c.283G>A) pathogenic?

EBP p.Ala95Thr (c.283G>A) is classified Uncertain significance in EBP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0938); Very rare (popmax 0.00435%, amr); Associated with X-linked chondrodysplasia punctata 2.

What condition is associated with EBP p.Ala95Thr (c.283G>A)?

EBP p.Ala95Thr (c.283G>A) is associated with X-linked chondrodysplasia punctata 2, MEND syndrome (ClinVar).

How common is EBP p.Ala95Thr (c.283G>A) in the general population?

EBP p.Ala95Thr (c.283G>A) is very rare (popmax 0.00435%, amr) (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.Ala95Thr (c.283G>A)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

EBP p.Ala95Thr

c.283G>A · rs2147154752 · VCV1330409

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked chondrodysplasia punctata 2

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -5.14	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 2.8	GERP 1, phastCons 1
Overall
CADD	18.81	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00435% Admixed American · 2/45,984 alleles

Filtering AF 0.000721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000182% 2/1,097,965 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.Ala95Thr
Coding: c.283G>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs2147154752
Type: single nucleotide variant
Location: chrX:48524054 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 95: 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

SH3D19 p.Ser95= Likely benign ★ 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-ala95thr (accessed [today's date]).

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