Is EBPL p.Pro180Ser (c.538C>T) pathogenic?

EBPL p.Pro180Ser (c.538C>T) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: ambiguous (0.4684); Ultra-rare (popmax 0.0187%, afr).

How common is EBPL p.Pro180Ser (c.538C>T) in the general population?

EBPL p.Pro180Ser (c.538C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about EBPL p.Pro180Ser (c.538C>T)?

AlphaMissense predicts ambiguous (score 0.4684) — an in-silico prediction, not a clinical call.

EBPL p.Pro180Ser

c.538C>T · VCV3506400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4684 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4684	ambiguous
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -13.55	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 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	27.7	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 0.0187% African / African-American · 14/74,974 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00167% 27/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,355
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000847%	118,001

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.Pro180Ser
Coding: c.538C>T
MANE Select: NM_032565
Type: single nucleotide variant
Location: chr13:49661051 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 180: 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-pro180ser (accessed [today's date]).

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