Is EBP p.Arg147His (c.440G>A) pathogenic?

EBP p.Arg147His (c.440G>A) is classified Pathogenic in EBP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-25). AlphaMissense: ambiguous (0.4526); Absent from gnomAD v4.1; Associated with EBP-related disorders.

What condition is associated with EBP p.Arg147His (c.440G>A)?

EBP p.Arg147His (c.440G>A) is associated with EBP-related disorders, MEND syndrome, X-linked chondrodysplasia punctata 2 (ClinVar).

How common is EBP p.Arg147His (c.440G>A) in the general population?

EBP p.Arg147His (c.440G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Arg147His (c.440G>A)?

AlphaMissense predicts ambiguous (score 0.4526) — an in-silico prediction, not a clinical call.

EBP p.Arg147His

c.440G>A · rs28935174 · VCV11492

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4526 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

EBP-related disorders

Computational evidence

Protein change
AlphaMissense	0.4526	ambiguous
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -9.25	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1
Overall
CADD	24.5	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.Arg147His
Coding: c.440G>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs28935174
Type: single nucleotide variant
Location: chrX:48527256 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 147: the 'disordered' region

Full EBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBP-related disorders

Also linked: MEND syndrome X-linked chondrodysplasia punctata 2

Similar variants

EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same condition
EBP p.Arg110Ter 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
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-arg147his (accessed [today's date]).

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