Is EFHC1 p.Pro455= (c.1365T>C) pathogenic?

EFHC1 p.Pro455= (c.1365T>C) is classified Uncertain significance in EFHC1 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 8.47e-05%, nfe); Associated with juvenile myoclonic epilepsy.

What condition is associated with EFHC1 p.Pro455= (c.1365T>C)?

EFHC1 p.Pro455= (c.1365T>C) is associated with juvenile myoclonic epilepsy (ClinVar).

How common is EFHC1 p.Pro455= (c.1365T>C) in the general population?

EFHC1 p.Pro455= (c.1365T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Juvenile myoclonic epilepsy inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

EFHC1 p.Pro455=

c.1365T>C · rs1581846971 · VCV830045

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

juvenile myoclonic epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.066	GERP -3.5, phastCons 0.73
Overall
CADD	7.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 6.84e-05% 1/1,461,850 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: EFHC1
Protein: p.Pro455=
Coding: c.1365T>C
MANE Select: NM_018100
dbSNP: rs1581846971
Type: single nucleotide variant
Location: chr6:52479123 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 455: the dm10 3 domain

Full EFHC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

juvenile myoclonic epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Juvenile myoclonic epilepsy (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adolescent, Childhood

Similar variants

EFHC1 p.Pro455Arg Uncertain significance ★ ⚠ same residue
EFHC1 p.Pro455Ser Uncertain significance ★ ⚠ same residue
EFHC1 p.Arg294Cys Uncertain significance ★★ ⚠ same condition
EFHC1 p.Asn304Ser Uncertain significance ★★ ⚠ same condition
EFHC1 p.Asn55Lys Uncertain significance ★★ ⚠ same condition
EFHC1 p.Tyr631Cys Uncertain significance ★★ ⚠ same condition
EFHC1 p.Val273Leu Uncertain significance ★★ ⚠ same condition
EFHC1 c.573+10A>G Benign/Likely benign ★★ same condition

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/efhc1-p-pro455 (accessed [today's date]).

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