Is EBP p.Ala54Val (c.161C>T) pathogenic?

EBP p.Ala54Val (c.161C>T) is classified Uncertain significance in EBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-29). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.000447%, nfe).

How common is EBP p.Ala54Val (c.161C>T) in the general population?

EBP p.Ala54Val (c.161C>T) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about EBP p.Ala54Val (c.161C>T)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

EBP p.Ala54Val

c.161C>T · rs2061771576 · VCV2673228

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP 2, phastCons 0.98
Overall
CADD	16.55	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 0.000447% European (non-Finnish) · 4/895,513 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000364% 4/1,098,263 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.Ala54Val
Coding: c.161C>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs2061771576
Type: single nucleotide variant
Location: chrX:48523932 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 54: the 'disordered' region

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

Similar variants

EBP p.Ala54= Likely benign ★ same residue
EBP p.Ala54fs Likely pathogenic ★ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
EBP p.Arg110Ter Pathogenic ★★ same type
EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Arg147His Pathogenic ★★ ⚠ same type
EBP p.Arg62Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same type

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-ala54val (accessed [today's date]).

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