Is EBPL p.Val177Phe (c.529G>T) pathogenic?

EBPL p.Val177Phe (c.529G>T) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.1665); Very rare (popmax 0.00334%, amr).

How common is EBPL p.Val177Phe (c.529G>T) in the general population?

EBPL p.Val177Phe (c.529G>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about EBPL p.Val177Phe (c.529G>T)?

AlphaMissense predicts likely benign (score 0.1665) — an in-silico prediction, not a clinical call.

EBPL p.Val177Phe

c.529G>T · rs1029257207 · VCV2336468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1665	likely benign
REVEL	0.846	moderately pathogenic-leaning
SaProt	LLR -9.31	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 2,093 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	23.8	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 0.00334% Admixed American · 2/59,968 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,984
European (non-Finnish)	0.000169%	590,023

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.Val177Phe
Coding: c.529G>T
MANE Select: NM_032565
dbSNP: rs1029257207
Type: single nucleotide variant
Location: chr13:49661060 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 177: 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-val177phe (accessed [today's date]).

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