Is EBPL p.Ala89Val (c.266C>T) pathogenic?

EBPL p.Ala89Val (c.266C>T) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0893); Very rare (popmax 0.00667%, afr).

How common is EBPL p.Ala89Val (c.266C>T) in the general population?

EBPL p.Ala89Val (c.266C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about EBPL p.Ala89Val (c.266C>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

EBPL p.Ala89Val

c.266C>T · rs893014688 · VCV3086882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -5.76	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 4.1	GERP -1.8, phastCons 0.82
Regional constraint	o/e 1.02	unconstrained · MANE · 28 kb · p 0.82 · regional, not allelic
Overall
CADD	16.83	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 0.00667% African / African-American · 5/74,918 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000496% 8/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,984
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	8.47e-05%	1,180,020

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.Ala89Val
Coding: c.266C>T
MANE Select: NM_032565
dbSNP: rs893014688
Type: single nucleotide variant
Location: chr13:49663171 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 89: 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-ala89val (accessed [today's date]).

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