Is EBP p.Arg52Cys (c.154C>T) pathogenic?

EBP p.Arg52Cys (c.154C>T) is classified Benign/Likely benign in EBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-04). AlphaMissense: likely benign (0.1002); Ultra-rare (popmax 0.0351%, afr); Associated with Inborn genetic diseases.

What condition is associated with EBP p.Arg52Cys (c.154C>T)?

EBP p.Arg52Cys (c.154C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EBP p.Arg52Cys (c.154C>T) in the general population?

EBP p.Arg52Cys (c.154C>T) is ultra-rare (popmax 0.0351%, afr) (gnomAD).

What do computational predictors say about EBP p.Arg52Cys (c.154C>T)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

EBP p.Arg52Cys

c.154C>T · rs782775797 · VCV1164233

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.46	indeterminate
SaProt	LLR -9.99	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 0.83	GERP -0.032, phastCons 0.32
Overall
CADD	16.5	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

Grpmax group 0.0351% African / African-American · 20/56,937 alleles

Filtering AF 0.0233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.00182% 22/1,209,275 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0351%	2,847
Admixed American	0.00219%	45,622
Remaining individualsnot grpmax-eligible	0.0021%	47,590

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.Arg52Cys
Coding: c.154C>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs782775797
Type: single nucleotide variant
Location: chrX:48523925 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 52: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBP p.Arg52Gly Uncertain significance ★ ⚠ same residue
EBP p.Gly173Arg Uncertain significance ★★ ⚠ same condition
EBP p.Gly177Arg Uncertain significance ★★ ⚠ same condition
EBP p.Arg171His Benign/Likely benign ★★ same condition
EBP c.301+3G>C Conflicting classifications of pathogenicity ★ same condition
EBP p.Arg142His Uncertain significance ★ ⚠ same condition
EBP p.Asn4Ile Uncertain significance ★ ⚠ same condition
EBP p.Cys127Ser Uncertain significance ★ ⚠ 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-arg52cys (accessed [today's date]).

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