Is EBPL p.Trp176Arg (c.526T>A) pathogenic?

EBPL p.Trp176Arg (c.526T>A) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely pathogenic (0.8043); Very rare (popmax 0.00364%, nfe).

How common is EBPL p.Trp176Arg (c.526T>A) in the general population?

EBPL p.Trp176Arg (c.526T>A) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about EBPL p.Trp176Arg (c.526T>A)?

AlphaMissense predicts likely pathogenic (score 0.8043) — an in-silico prediction, not a clinical call.

EBPL p.Trp176Arg

c.526T>A · rs747612403 · VCV3086885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8043	likely pathogenic · top 2% in EBPL
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -12.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 2,093 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00364% European (non-Finnish) · 43/1,180,022 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00266% 43/1,614,024 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: EBPL
Protein: p.Trp176Arg
Coding: c.526T>A
MANE Select: NM_032565
dbSNP: rs747612403
Type: single nucleotide variant
Location: chr13:49661063 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 176: the expera domain

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

Similar variants

EBPL p.Ala107Ser Uncertain significance ★ ⚠ same type
EBPL p.Ala107Thr Uncertain significance ★ ⚠ same type
EBPL p.Ala11Gly Uncertain significance ★ ⚠ same type
EBPL p.Ala23Glu Uncertain significance ★ ⚠ same type
EBPL p.Ala27Thr Uncertain significance ★ ⚠ same type
EBPL p.Ala38Val Uncertain significance ★ ⚠ same type
EBPL p.Ala39Val Uncertain significance ★ ⚠ same type
EBPL p.Ala43Gly Uncertain significance ★ ⚠ 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/ebpl-p-trp176arg (accessed [today's date]).

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