Is CACNA1E p.Phe341= (c.1023T>C) pathogenic?

CACNA1E p.Phe341= (c.1023T>C) is classified Benign/Likely benign in CACNA1E (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). Rare (popmax 0.191%, nfe); Associated with developmental and epileptic encephalopathy, 69.

What condition is associated with CACNA1E p.Phe341= (c.1023T>C)?

CACNA1E p.Phe341= (c.1023T>C) is associated with developmental and epileptic encephalopathy, 69 (ClinVar).

How common is CACNA1E p.Phe341= (c.1023T>C) in the general population?

CACNA1E p.Phe341= (c.1023T>C) is rare (popmax 0.191%, nfe) (gnomAD).

CACNA1E p.Phe341=

c.1023T>C · rs200603172 · VCV1167748

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.191%, nfe)

Conditions

developmental and epileptic encephalopathy, 69

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 1.1	GERP -1.3, phastCons 1
Overall
CADD	10.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.191% European (non-Finnish) · 2,252/1,179,744 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.207% 3,347/1,613,850 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.41%	71
European (non-Finnish)grpmax	0.191%	524
Remaining individualsnot grpmax-eligible	0.162%	619
Admixed American	0.0816%	1,225
African / African-American	0.028%	3,574
South Asian	0.0231%	4,337

Finnish 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: CACNA1E
Protein: p.Phe341=
Coding: c.1023T>C
MANE Select: NM_001205293
dbSNP: rs200603172
Type: single nucleotide variant
Location: chr1:181651409 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.56 · 5 PDB
Residue 341: an α-helix

Full CACNA1E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 69 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACNA1E p.Ala702Thr Pathogenic/Likely pathogenic ★★ same condition
CACNA1E p.Gly348Arg Pathogenic/Likely pathogenic ★★ same condition
CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same condition
CACNA1E p.Ile603Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
CACNA1E p.Ile701Val Pathogenic ★★ ⚠ same condition
CACNA1E p.Leu228Pro Pathogenic/Likely pathogenic ★★ same condition
CACNA1E p.Phe698Leu Pathogenic/Likely pathogenic ★★ same condition
CACNA1E c.3719+1G>A 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/cacna1e-p-phe341 (accessed [today's date]).

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