Is EBP p.Val163Leu (c.487G>T) pathogenic?

EBP p.Val163Leu (c.487G>T) is classified Uncertain significance in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). AlphaMissense: likely benign (0.1459); Very rare (popmax 0.0019%, nfe).

How common is EBP p.Val163Leu (c.487G>T) in the general population?

EBP p.Val163Leu (c.487G>T) is very rare (popmax 0.0019%, nfe) (gnomAD).

What do computational predictors say about EBP p.Val163Leu (c.487G>T)?

AlphaMissense predicts likely benign (score 0.1459) — an in-silico prediction, not a clinical call.

EBP p.Val163Leu

c.487G>T · rs1354655797 · VCV2965651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0019%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1459	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -6.68	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 -0.13	GERP -4.2, phastCons 0.004
Overall
CADD	15.13	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 0.0019% European (non-Finnish) · 17/894,931 alleles

Filtering AF 0.00116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000946%

Overall 0.00141% 17/1,209,472 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.Val163Leu
Coding: c.487G>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs1354655797
Type: single nucleotide variant
Location: chrX:48528251 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 163: the 'disordered' region

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

Similar variants

EBP p.Val163Ala Uncertain significance ★ ⚠ 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
EBP p.Gly161Arg 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-val163leu (accessed [today's date]).

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