Is EBPL p.Val53Ala (c.158T>C) pathogenic?

EBPL p.Val53Ala (c.158T>C) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.3731); Ultra-rare (popmax 0.0728%, sas).

How common is EBPL p.Val53Ala (c.158T>C) in the general population?

EBPL p.Val53Ala (c.158T>C) is ultra-rare (popmax 0.0728%, sas) (gnomAD).

What do computational predictors say about EBPL p.Val53Ala (c.158T>C)?

AlphaMissense predicts ambiguous (score 0.3731) — an in-silico prediction, not a clinical call.

EBPL p.Val53Ala

c.158T>C · VCV4246299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0728%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3731	ambiguous
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -10.49	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 28 kb · p 0.82 · regional, not allelic
Overall
CADD	25.6	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 0.0728% South Asian · 40/54,982 alleles

Filtering AF 0.0549% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00314% 44/1,399,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0728%	1,375
Remaining individualsnot grpmax-eligible	0.00575%	17,386
European (non-Finnish)	9.32e-05%	1,072,986

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.Val53Ala
Coding: c.158T>C
MANE Select: NM_032565
Type: single nucleotide variant
Location: chr13:49691267 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 53: 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-val53ala (accessed [today's date]).

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