Is EFHC1 p.Ile367fs (c.1098del) pathogenic?

EFHC1 p.Ile367fs (c.1098del) is classified Uncertain significance in EFHC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-30). Very rare (popmax 0.00119%, nfe); Associated with myoclonic epilepsy, juvenile, susceptibility to, 1.

What condition is associated with EFHC1 p.Ile367fs (c.1098del)?

EFHC1 p.Ile367fs (c.1098del) is associated with myoclonic epilepsy, juvenile, susceptibility to, 1 (ClinVar).

How common is EFHC1 p.Ile367fs (c.1098del) in the general population?

EFHC1 p.Ile367fs (c.1098del) is very rare (popmax 0.00119%, nfe) (gnomAD).

EFHC1 p.Ile367fs

c.1098del · rs1181131881 · VCV1482836

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Conditions

myoclonic epilepsy, juvenile, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.7	GERP -3.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,014 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00116% 17/1,461,726 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)grpmax	0.00119%	84,286

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile367fs
Coding: c.1098del
MANE Select: NM_018100
dbSNP: rs1181131881
Type: Deletion
Location: chr6:52465076 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB

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

Disease context

myoclonic epilepsy, juvenile, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFHC1 p.Asp228fs Uncertain significance ★★ same condition
EFHC1 p.Gln395fs Uncertain significance ★★ same condition
EFHC1 p.Glu391fs Uncertain significance ★ same condition
EFHC1 p.Ile122_Tyr123del Uncertain significance ★ same condition
EFHC1 c.1841_1851+13del Likely benign ★ same condition
EFHC1 c.723+66del Benign ★ same condition
EFHC1 p.Ala445Thr Uncertain significance ★★ ⚠ same condition
EFHC1 p.Ala529Glu Uncertain significance ★★ ⚠ 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-ile367fs (accessed [today's date]).

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